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A new fossil species, Cedrus anatolica n. sp., is described from the early Miocene Hancili Formation of Turkey. All analyses were performed on the thin sections housed at Istanbul University – Cerrahpasa. The new species was interpreted as having the closest affinity with the modern Mediterranean species Cedrus atlantica (Endlicher) Manetti ex Carriere and Cedrus libani Richard. The evolutionary line shows some changes in wood anatomy. From the early Cretaceous to the early Miocene, the pits on the tangential walls of the tracheids gradually decreased, the height of rays increased and the number of epithelial cells in the traumatic resin canals increased slightly. These features are similar in three modern species; other wood anatomical features are also quite stable among the new fossil and modern species.

The two-dimensional (2D) affinity between protein molecules across contacting cells is a key parameter regulating and initiating several cellular processes. However, measuring 2D affinity can be challenging and experimental data are limited. In addition, the obtained 2D affinities are typically averaged over the cell population. We here present a method to measure 2D affinity on single cells binding to polyhistidine-tagged fluorescent ligands anchored to a supported lipid bilayer (SLB). By decreasing the density of ligands in the SLB using imidazole a new steady-state accumulation in the contact is obtained, and from this change, both the 2D affinity and the number of receptors on the cell can be determined. The method was validated on an SLB containing rat CD2 binding to the rat CD48 mutant T92A expressed on Jurkat T cells. The addition of imidazole did not influence the average 2D affinity (1/Kd), and the spread in affinities within the cell population was low, Kd = 4.9 ± 0.9 molecules/μm2 (mean ± SD), despite an order of magnitude spread in ligand accumulation due to differences in receptor density. It was also found that cell contact size increased both with ligand density and with the number of receptors per cell, but that the contact size stayed approximately constant when lowering the ligand density, above a density of around 10 rCD2 molecules/μm2, after the contact first had formed, indicative of a heterogeneous process. In summary, this method not only allows for single-cell affinities to be measured, but it can also reduce measurement and analysis time and improve measurement accuracy. Due to the low spread in 2D Kd within the cell population, the analysis can further be restricted to the cells showing the strongest binding, paving the way for using this method to study weak binding events.

Weakly supervised temporal action detection aims at localizing actions with only video-level labels rather than lots of frame-level labels. To this end, previous methods train a classification network for mining discernible action frames as detection results. However, the classification network is known to only concentrate on local discernible frames rather than the entire action instance. Therefore, substantial numbers of indiscernible action frames are not detected and the detection results are incomplete. To alleviate this issue, we propose a novel method to facilitate the detection of indiscernible frames based on learning frame-level affinities. In the proposed method, we design a network (named Affinity Network) for predicting affinities between pairs of adjacent frames. Then, the affinities are used as transition probabilities to propagate local responses to indiscernible frames. As a result, the responses of indiscernible frames can be enhanced and the detection of them can be facilitated. For learning the network, we propose strategies to synthesize frame-pair and video-pair training samples, which are conducive to learn frame-level affinities with only video-level labels. The experimental results on THUMOS14 dataset and ActivityNet1.2 dataset show that the detection performance of our framework outperforms most previous weakly supervised action detection methods, and is even as competitive as some fully supervised action detection methods.

The SLC1 family includes seven members divided into two groups, namely, EAATs and ASCTs, that share similar 3D architecture; the first one includes high-affinity glutamate transporters, and the second one includes SLC1A4 and SLC1A5, known as ASCT1 and ASCT2, respectively, responsible for the traffic of neutral amino acids across the cell plasma membrane. The physiological role of ASCT1 and ASCT2 has been investigated over the years, revealing different properties in terms of substrate specificities, affinities, and regulation by physiological effectors and posttranslational modifications. Furthermore, ASCT1 and ASCT2 are involved in pathological conditions, such as neurodegenerative disorders and cancer. This has driven research in the pharmaceutical field aimed to find drugs able to target the two proteins.This review focuses on structural, functional, and regulatory aspects of ASCT1 and ASCT2, highlighting similarities and differences.

A new shell-bearing organism with preserved soft tissue, Armilimax pauljamisoni n. gen. n. sp., is reported from the middle Cambrian (Miaolingian: Wuliuan) Miners Hollow locality of the Spence Shale of northern Utah. The described organism is known from a single articulated specimen and preserves a prominent shell, a slug-like body, as well as a U-shaped digestive tract. Its overall appearance is similar to halkieriids, but it does not preserve sclerites. The possible affinities of the new taxon and potential reasons for the presence of a U-shaped gut are discussed. Armilimax pauljamisoni is the first shell-bearing animal of its kind from the Great Basin and extends the diversity of body plans in the Spence Shale Fossil-Lagerstatte.

Novel degraded potassium channel-modulatory peptides were recently found in thermally processed scorpions, but their pharmacological properties remain unclear. Here, we identified a full-length scorpion toxin (i.e., BmKcug2) and its four truncated analogs (i.e., BmKcug2-P1, BmKcug2-P2, BmKcug2-P3 and BmKcug2-P4) with three conserved disulfide bonds in processed scorpion medicinal material by mass spectrometry. The pharmacological experiments revealed that the recombinant BmKcug2 and BmKcug2-P1 could selectively inhibit the human Kv1.2 and human Kv1.3 potassium channels, while the other three analogs showed a much weaker inhibitory effect on potassium channels. BmKcug2 inhibited hKv1.2 and hKv1.3 channels, with IC50 values of 45.6 ± 5.8 nM and 215.2 ± 39.7 nM, respectively, and BmKcug2-P1 inhibited hKv1.2 and hKv1.3, with IC50 values of 89.9 ± 9.6 nM and 1142.4 ± 64.5 nM, respectively. The chromatographic analysis and pharmacological properties of BmKcug2 and BmKcug2-P1 boiled in water for different times further strongly supported their good thermal stability. Structural and functional dissection indicated that one amino acid, i.e., Tyr36, determined the differential affinities of BmKcug2 and four BmKcug2 analogs. Altogether, this research investigated the different pharmacological properties of BmKcug2 and its truncated analogs, and the findings highlighted the diversity of K+ channel blockers from various scorpion species through thermal processing.

Protein disulfide isomerase (PDI) is an important molecular chaperone capable of facilitating protein folding in addition to catalyzing the formation of a disulfide bond. To better understand the distinct substrate-screening principles of Pichia pastoris PDI (Protein disulfide isomerase) and the protective role of PDI in amyloidogenic diseases, we investigated the expression abundance and intracellular retention levels of three archetypal amyloidogenic disulfide bond-free proteins (Aβ42, α-synuclein (α-Syn) and SAA1) in P. pastoris GS115 strain without and with the overexpression of PpPDI (P. pastoris PDI). Intriguingly, amyloidogenic Aβ42 and α-Syn were detected only as intracellular proteins whereas amyloidogenic SAA1 was detected both as intracellular and extracellular proteins when these proteins were expressed in the PpPDI-overexpressing GS115 strain. The binding between PpPDI and each of the three amyloidogenic proteins was investigated by molecular docking and simulations. Three different patterns of PpPDI-substrate complexes were observed, suggesting that multiple modes of binding might exist for the binding between PpPDI and its amyloidogenic protein substrates, and this could represent different specificities and affinities of PpPDI toward its substrates. Further analysis of the proteomics data and functional annotations indicated that PpPDI could eliminate the need for misfolded proteins to be partitioned in ER-associated compartments.

Selective separation of CO2/CH4 and C2H2/CH4 are promising for their high-purity industrial demand and scientific research on account of the similar molecular radius and physical properties. In this work, a unique 3D microporous MOF material [Cu(SiF6)(sdi)2]·solvents (1, sdi = 1,1′-sulfonyldiimidazole) was successfully constructed by cross-linking 1D coordination polymer chains. The dense functional active sites on the inner walls of the channel of 1a can provide strong binding affinities to CO2, C2H2, and thus effectively improve the gas separation performance of CO2/CH4 and C2H2/CH4.

Graphical abstract, The neuropeptide vasopressin (VP) and its three G protein-coupled receptors (V1aR, V1bR and V2R) are of high interest in a wide array of drug discovery programs. V1aR is of particular importance due to its cardiovascular functions and diverse roles in the central nervous system. The structure–activity relationships underpinning ligand-receptor interactions remain however largely unclear, hindering rational drug design. This is not least due to the high structural flexibility of VP in its free as well as receptor-bound states. In this work, we developed a novel approach to reveal features of conformational selectivity upon VP-V1aR complex formation. We employed virtual screening strategies to probe VP’s conformational space for transiently adopted structures that favor binding to V1aR. To this end, we dissected the VP conformational space into three sub-ensembles, each containing distinct structural sets for VP’s three-residue C-terminal tail. We validated the computational results with experimental nuclear magnetic resonance (NMR) data and docked each sub-ensemble to V1aR. We observed that the conformation of VP’s three-residue tail significantly modulated the complex dissociation constants. Solvent-exposed and proline trans-configured VP tail conformations bound to the receptor with three-fold enhanced affinities compared to compacted or cis-configured conformations. The solvent-exposed and more flexible structures facilitated unique interaction patterns between VP and V1aR transmembrane helices 3, 4, and 6 which led to high binding energies. The presented “virtual conformational space screening” approach, integrated with NMR spectroscopy, thus enabled identification and characterization of a conformational selection-type complex formation mechanism that confers novel perspectives on targeting the VP-V1aR interactions at the level of the encounter complex – an aspect that opens novel research avenues for understanding the functionality of the evolutionary selected conformational properties of VP, as well as guidance for ligand design strategies to provide more potent and selective VP analogues.

Although conformational dynamics of RNA molecules are potentially important in microRNA (miRNA) processing, the role of the protein binding partners in facilitating the requisite structural changes is not well understood. In previous work, we and others have demonstrated that nonduplex structural elements and the conformational flexibility they support are necessary for efficient RNA binding and cleavage by the proteins associated with the two major stages of miRNA processing. However, recent studies showed that the protein DGCR8 binds primary miRNA and duplex RNA with similar affinities. Here, we study RNA binding by a small recombinant construct of the DGCR8 protein and the RNA conformation changes that result. This construct, the DGCR8 core, contains two double-stranded RNA-binding domains (dsRBDs) and a C-terminal tail. To assess conformational changes resulting from binding, we applied small-angle x-ray scattering with contrast variation to detect conformational changes of primary-miR-16-1 in complex with the DGCR8 core. This method reports only on the RNA conformation within the complex and suggests that the protein bends the RNA upon binding. Supporting work using smFRET to study the conformation of RNA duplexes bound to the core also shows bending. Together, these studies elucidate the role of DGCR8 in interacting with RNA during the early stages of miRNA processing.

Post-translational modification with one of the isoforms of the small ubiquitin-like modifier (SUMO) affects thousands of proteins in the human proteome. The binding of SUMO to SUMO interacting motifs (SIMs) can translate the SUMOylation event into functional consequences. The E3 ubiquitin ligase RNF4 contains multiple SIMs and connects SUMOylation to the ubiquitin pathway. SIM2 and SIM3 of RNF4 were shown to be the most important motifs to recognize SUMO chains. However, the study of SIM-SUMO complexes is complicated by their typically low affinity and variable binding of the SIMs in parallel and antiparallel orientations. We investigated properties of complexes formed by SUMO3 with peptides containing either SIM2 or SIM3 using molecular dynamics simulations. The affinities of the complexes were determined using a state-of-the-art free energy protocol and were found to be in good agreement with experimental data, thus corroborating our method. Long unrestrained simulations allowed a new interpretation of experimental results regarding the structure of the SIM-SUMO interface. We show that both SIM2 and SIM3 bind SUMO3 in parallel and antiparallel orientations and identified main interaction sites for acidic residues flanking the SIM. We noticed unusual SIM-SUMO interfaces in a previously reported NMR structure (PDB: 2mp2) of a complex formed by a SUMO3 dimer with the bivalent SIM2-SIM3 peptide. Computational determination of the individual SIM-SUMO affinities based on these structural arrangements yielded significantly higher dissociation constants. To our knowledge, our approach adds new opportunities to characterize individual SIM-SUMO complexes and suggests that further studies will be necessary to understand these interactions when occurring in multivalent form.

G protein-coupled receptors (GPCRs) represent the largest class of “druggable” proteins in the human genome. For more than a decade, crystal structures and, more recently, cryoEM structures of GPCR complexes have provided unprecedented insight into GPCR drug binding and cell signaling. Nevertheless, structure determination of receptors in complexes with weakly binding molecules or complex polypeptides remains especially challenging, including for hormones, many of which have so far eluded researchers. Nuclear magnetic resonance (NMR) spectroscopy has emerged as a promising approach to determine structures of ligands bound to their receptors and to provide insights into the dynamics and pharmacokinetics of GPCR-bound drugs. The capability to investigate compounds with weak binding affinities has also been leveraged in NMR applications to identify novel lead compounds in drug screening campaigns. We review recent structural biology studies of GPCR ligands by NMR, highlighting new methodologies enabling studies of GPCRs with native sequences and in native-like membrane environments that provide insights into important drugs and endogenous ligands.

Oligonucleotide RA36 contains two G-quadruplex modules with thrombin binding aptamer sequence GGTTGGTGTGGTTGG. Each of the modules potentially can bind thrombin while differing in functional activity. Despite that, previously published studies report a single dissociation constant for the thrombin:RA36 complex, which value varies widely. Here we address this discrepancy using electrophoretic mobility shift assay. Our results reveal that the interaction between RA36 and thrombin is a two-stage process. The two modules have different affinities for thrombin, which explains the discrepancy in the published data.

A series of well-defined N-glycosylated IgG4-Fc variants were utilized to investigate the effect of glycan structure on their physicochemical properties (conformational stability and photostability) and interactions with an Fc γ receptor IIIA (FcγRIIIA). High mannose (HM, GlcNAc2Man(8+n) [n = 0-4]), Man5 (GlcNAc2Man5), GlcNAc1, and N297Q IgG4-Fc were prepared in good quality. The physical stability of these IgG4-Fc variants was examined with differential scanning calorimetry and intrinsic fluorescence spectroscopy. Photostability was assessed after photoirradiation between 295 and 340 nm (λ max = 305 nm), and HPLC-MS/MS analysis of specific products was performed. The size of glycans at Asn297 affects the yields of light-induced Tyr side-chain fragmentation products, where the yields decreased in the following order: N297Q > GlcNAc1 > Man5 > HM. These yields correlate with the thermal stability of the glycoforms. The HM and Man5 glycoforms display increased affinity for FcγRIIIA by at least 14.7-fold compared with GlcNAc1 IgG4-Fc. The affinities measured for the HM and Man5 IgG4-Fc (0.39-0.52 μM) are similar to those measured for fucosylated IgG1. Dependent on the mechanisms of action of IgG4 therapeutics, such glycoforms may need to be carefully monitored. The nonglycosylated N297Q IgG4-Fc did not present measurable affinity to FcγRIIIA.

ATP is the universal energy currency for all cells but has cellular concentrations of 2–12 mM, much higher than required for its classic functions. RNA-recognition motif (RRM) constitutes one of the most abundant domains in eukaryotes and most heterogeneous nuclear ribonucleoproteins (hnRNP) contain RRM domains which not only mediate direct interactions with nucleic acids, but whose aggregation/fibrillation is the pathological hallmark of various human diseases. Here, by NMR and molecular docking, ATP has been decoded to bind TDP-43 two tandem RRM domains with distinctive types of interactions, thus resulting in diverse affinities. Most strikingly, the binding of ATP enhances thermodynamic stability of TDP-43 RRM domains and inhibits ALS-/AD-associated fibrillation. Together, ATP is a cryptic binder of RRM-containing proteins which generally safeguards functional phase separation from transforming into pathological aggregation/fibrillation associated with various diseases and ageing. Our study thus reveals a mechanism of ATP to control protein homeostasis by specific binding.

Quantitative structure–activity relationship (QSAR) and molecular docking studies were carried out on 4-Alkoxy-Cinnamic derivatives as potent anti-mycobacterium tuberculosis. Chemical structures of the molecules were optimized by employing Density Functional Theory and utilizing (B3LYP) with the 6-31G∗ basis set. Four models were generated by Genetic Function Approximation (GFA). Model one was selected as the optimum model based on validation parameters which were found to be significant with correlation coefficient (R2) of 0.980921, adjusted correlation coefficient (R2 adj) value of 0.97547 and Cross validation coefficient (Qcv2) value of 0.965244. External validations were employed to validate the chosen model and the model was found to have (R2test) of 0.8756 and Coefficient of determination for Y-randomization (c Rp2) value of 0.867578. The Molecular docking studies showed that the ligand 1,2,3,4,5 and 6 with better activities have higher bind affinities ranging from (−6.4 and −10.4 kcal/mol) which formed H-bonds and hydrophobic interactions with amino acid residues of mycobacterum tuberculosis (M. tuberculosis) DNA gyrase receptor. This research has shown that the binding affinities of these inhibitors were found to be better than the commercially sold anti-mycobacterium tuberculosis; enthambutol (−5.8 kcal/mol) and isoniazid (−5.3 kcal/mol). QSAR model generated and molecular docking results propose the direction for the design of new anti-tubercular agents with better activities against DNA gyrase. Keywords: Anti-tuberculosis, Binding affinity, Molecular docking, QSAR, Y-radomization

RNA-binding proteins TDP-43 and FUS play essential roles in pre-mRNA splicing, localization, granule formation and other aspects of RNA metabolism. Both proteins are implicated in neurodegenerative diseases amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD). Despite their apparent similarities, each protein has unique structural characteristics. Here we present the current structural understanding of RNA-binding and self-association mechanisms. Both globular and intrinsically disordered domains contribute to RNA binding, each with different specificities, affinities and kinetics. Self-associating Prion-like domains in each protein form multivalent interactions and labile cross-β structures. These interactions are modulated by distinctive additional domains including a globular oligomerization domain in TDP-43 and synergistic interactions with intrinsically disordered Arginine-Glycine rich domains in FUS. These insights contribute to a better understanding of native biological functions of TDP-43 and FUS and potential molecular pathways in neurodegenerative diseases.

Proteins interact with one another across a broad spectrum of affinities. Our understanding of the low end of this spectrum, as characterized by millimolar dissociation constants, relies on a handful of cases in which weak encounters have experimentally been identified. These weak interactions away from the specific target binding site can lead toward a higher-affinity complex. Recently, we detected weak encounters between two paralogous phosphotransferase pathways of Escherichia coli, which regulate various metabolic processes and stress responses. In addition to encounters that are known to occur between cognate proteins, i.e., those that can exchange phosphate groups with each other, surprisingly, encounters involving noncognates were also observed. It is not clear whether these “futile” encounters have a cooperative or competitive role. Using agent-based simulations, we find that the encounter complexes can be cooperative or competitive so as to increase or lower the effective binding affinity of the specific complex under different circumstances. This finding invites further questions into how organisms might exploit such low affinities to connect their signaling components.

Perexiflasca tayloriana, a widespread microfossil in the Lower Devonian Rhynie chert from Scotland, consists of a thin-walled cavity surrounded by a prominent sheath. A single tube extends from the cavity to the surface. Specimens occur singly or aggregated in decaying plant tissue and on fungi. Perexiflasca tayloriana has been attributed to the Chytridiomycota and interpreted as a sheathed zoosporangium. Here we report Perexiflasca ventricosa nov. sp., a fossil from the nearby coeval Windyfield chert that corresponds to P. tayloriana in basic organization, but possesses a distinctly larger cavity and wider tube, while the sheath is proportionally less extensive. The diagnosis and description of P. tayloriana are emended. The similarities between P. tayloriana and P. ventricosa nov. sp. render attribution also of P. ventricosa nov. sp. to the Chytridiomycota a plausible option, but features of sufficient clarity to permit reliable assignment are absent. Perexiflasca ventricosa nov. sp. expands the inventory of morphologically distinct microbial fossils from the Rhynie and Windyfield cherts.

More than 300 million people are suffering from depression, one of the civilization diseases in the 21st century. Serotonin 5-HT1AR and dopamine D2R play an important role in the treatment and pathogenesis of depression. Moreover, in recent years, the efficacy of dual 5-HT1A/D2 receptors ligands has been demonstrated in the fight against depression. In this work the new bulky arylpiperazine derivatives (LCAP) were synthesized in microwave radiation field. The affinities for the selected serotonin (5-HT1A,5-HT2A,5-HT6,5-HT7) and dopamine (D2) receptors have been evaluated in vitro. Compounds 5.3a, 5.4, 5.1c, 5.3d, 5.2a are promising dual 5-HT1AR/D2R ligands. The SAR analysis were additionally supported with molecular docking studies.

Vascular endothelial growth factor receptor 2 (VEGFR2) controls angiogenesis and is critically important for normal human development and cancer progression. A recent finding that VEGFR2 can dimerize in the absence of ligand raises the question whether VEGF binds to either VEGFR2 monomers or dimers or to both. Although VEGF–VEGFR2 effective binding constants have been measured, these prior measurements have not discriminated between the association state of the receptor. Because ligand binding is coupled to receptor dimerization, this coupling lends complexity to a seemingly straightforward problem. Here, we unravel this complexity by applying a rigorous thermodynamics approach and performing binding measurements over a broad range of receptor and ligand concentrations. By applying a global fitting procedure to a large data set, we reveal a 45-fold difference between VEGF binding affinities for monomeric and dimeric forms of VEGFR2.

Photoswitchable catalysis involves alteration in the intrinsic catalytic properties of an active species through a reversible photochemical transformation. Herein, we report dihydroazulene-vinylheptafulvene (DHA-VHF) based photoswitchable frustrated Lewis pairs (FLPs) for reversible hydrogen activation. The dihydroazulene-vinylheptafulvene moieties here do not act as template to control the catalytic activity, rather the core part of the catalyst. The rational design principle involves evaluation of proton and hydride affinities of Lewis acids (borane) and base (phosphine and amine) functionalities installed on dihydroazulene-vinylheptafulvene photoswitch pair. Significant differences are observed between open VHF and closed DHA for proton and hydride affinities, and these differences are explained by geometric and electronic factors. The individual proton and hydride affinities are utilized to logically formulate best relative positions of both Lewis acid and base on a single molecule in order to activate one H2 molecule per photochrome. For our judiciously designed FLPs, the behavior of phosphine based FLP resembles to that of amine based FLPs at position 2 and 3, however they differ at position 8a. For amine based FLP, the energy released for hydrogen splitting is higher than DHA for all positions (2, 3, 8a) whereas in VHF phosphine based FLP, the energy released on H2 splitting in VHF is lower than that of DHA at position 8a. Moreover, hydrogen splitting is studied on couple of cautiously selected molecules based on the proton and hydride affinities. The activation barriers for hydrogen splitting in VHFs are about 8–10 kcal mol−1 lower than the corresponding barriers in DHAs, chiefly due to the higher hydride and proton affinities.

Flavonoids possess the inhibition ability against tyrosinase. Here, the effects of flavonoids structure on inhibitory activity and binding affinity of tyrosinase were investigated. The results showed that the hydroxy groups of 5C−OH, 4′C−OH and 5′C−OH of flavonoids were in favor of forming hydrogen bond with the amino acid residues of tyrosinase, which played a crucial role in the binding and interaction between flavonoids and tyrosinase. Different groups of flavonoids exhibited different influences on tyrosinase inhibitory activity and binding affinity. The hydroxylation at C3′ position of flavonoids increased affinities for tyrosinase, whereas the inhibitory activities went downward and upward for flavone and flavonol, respectively. The hydrogenation of the C2 = C3 double bond of flavones weakened inhibitory activities and strengthened affinities, which increased affinities of flavonols with downward and upward inhibitions. The decreased inhibitory activities and affinities can be realized by the hydroxylation of the C4′ and C5′ of flavonoids. Methylation of flavonoids decreased the inhibition while methoxylation of 5′C increased affinity and methylation of 4’−OH led to an increase in affinity. Glycosylation mainly induced the decline in both inhibitory activities and affinities of flavonoids. These findings may provide useful information for the structural modification of flavonoids as effective tyrosinase inhibitors.

Based on Nap-1, a Mcl-1/Bcl-2 dual inhibitor reported by our group, we carried out a structure-guided molecular design and structure-activity relationship (SAR) analysis to study structural features contributing to Mcl-1 binding selectivity and affinity. A series of derivatives of Nap-1 with various pharmacophores were synthesized and among them a dual Mcl-1/Bcl-2 inhibitor A4 with enhanced affinities (IC50 = 0.15 μM for Mcl-1, 0.43 μM for Bcl-2) and a selective Mcl-1 inhibitor B9 with a 20-fold selectivity over Bcl-2 (IC50 = 0.51 μM vs 9.46 μM) were obtained by enzyme linked immunosorbent assay (ELISA). The SAR data and binding modes of A4 and B9 investigated by 2D-NMR derived docking study illustrated that p2 pockets exhibiting different geometry and binding features between Mcl-1 and Bcl-2 contribute to specific binding properties of Mcl-1. In addition, apoptosis-inducing potencies of A4 and B9 were consistent with their binding selectivity determined in vitro.

The influence of the biogeographical affinities of taxa on the spatial determinants of plant diversity remains largely unknown. I explored the spatial patterns of tropical and temperate plant diversity in Northwest Yunnan and their primary determinants. Generalized linear models (GLMs) and variance partitioning were used to investigate the influences of predictors. Temperate genus diversity significantly increased with latitude, whereas tropical genus diversity did not show any obvious latitudinal trends. Proportions of tropical genera decreased with latitude, whereas those of temperate genera were on the contrary. Environment heterogeneity explained higher percentage of the spatial variation of temperate genus diversity than for that of tropical genus diversity. It may imply that the influence of environment heterogeneity on plant diversity may depend on the taxa's biogeographic affinities, which might modify the exploitation of environment heterogeneity, though the flora diversification induced by the uplifting of the Tibet Plateau may also play important roles. Climate predictors explained higher percentages of variation in the proportions of tropical genera than for the variations in tropical genus diversity. It may suggest that compared with the associations between genus diversity with tropical affinities and climatic conditions, the associations between the proportions of tropical plants and climatic conditions might more accurately reflect niche conservatism of tropical plants in the study area.

Exoskeletal morphological structures of all extant genera currently included into Mastigitae are very well studied, whereas the larvae are poorly known. Larval morphology provides a valuable character system for phylogenetic reconstructions, and as all hitherto carried out analyses of Mastigitae were based on adult characters only, it is important to fill this major gap by studying immature stages. We here describe in detail the second- and third-instar larvae of the South African ant-like stone beetle Palaeostigus bifoveolatus, including chaetotaxic structures. We attempt to identify novel characters to distinguish larvae of Palaeostigus and Stenomastigus, and instar-specific features. The hypersetation found in P. bifoveolatus supports previous findings of close phylogenetic affinities between Mastigitae and Scydmaenini, and the tendency toward reduction of the antennomere III, from small to vestigial, is also consistent with the current phylogenetic hypotheses regarding these two groups within Scydmaeninae.

Cyanobacterial blooms are becoming a serious challenge across the globe due to changing climate and rainfall patterns as a consequence of human activities. In the present study, the fundamental interactions involved during the removal of Microcystin-LR (MCLR), one of the most commonly occurring cyanobacterial toxins, were investigated by employing strongly basic anion exchange (IX) resins. Several factors including the stoichiometric coefficients, competitive fractions and solute affinities were determined under various concentrations of inorganic ions and natural organic matter. The results indicated that suphates were the most competitive fractions with high affinity (α (affinity coefficient) values ~ 9) followed by nitrates (α ~ 4.7) and NOM fractions (α ~ 4.5, p 0.05). The Equivalent Background Concentration Mode (EBC), that arises from the Ideal Adsorption Solution Theory (IAST), indicated a competitive fraction of ~2 μeq/L NOM, which approximates to10% of the initial NOM concentrations, indicating a small fraction of the NOM resulting in the competitive effect. Further, studies with natural surface waters indicated that the MCLR uptake could be modeled using the IAST-EBC model and the IX resin could simultaneously removal of90% of NOM, inorganic ions and MCLR at resin dosages of 3.6 meq/L or higher.

Graphical abstract, Highlights • The receptor-binding domain proteins of both SARS-CoV-1 and SARS- CoV-2 spike proteins do bind to the cell receptor ACE2 with similar affinities although the latter is less specific. • The complexation of the receptor-binding domain proteins with ACE2 can happen at both acid and neutral pH regimes which probably indicates that the medium pH is not so relevant for the beginning of the viral cell invasion and should limit the clinical action of drugs like chloroquine. • The neutralizing monoclonal antibody CR3022 has shown the highest binding affinity under all studied conditions. • Amino acids substitutions for the antibody CR3022 are suggested to improve its binding affinity, and it now serves as a template to design other inhibitory molecules with higher and more specific affinities. • The interaction of the receptor-binding domain proteins with both the studied antibodies and ACE2 involves several common titratable amino acids as indicated by the map of the electrostatic epitopes., A new betacoronavirus named SARS-CoV-2 has emerged as a new threat to global health and economy. A promising target for both diagnosis and therapeutics treatments of the new disease named COVID-19 is the coronavirus (CoV) spike (S) glycoprotein. By constant-pH Monte Carlo simulations and the PROCEEDpKa method, we have mapped the electrostatic epitopes for four monoclonal antibodies and the angiotensin-converting enzyme 2 (ACE2) on both SARS-CoV-1 and the new SARS-CoV-2 S receptor binding domain (RBD) proteins. We also calculated free energy of interactions and shown that the S RBD proteins from both SARS viruses binds to ACE2 with similar affinities. However, the affinity between the S RBD protein from the new SARS-CoV-2 and ACE2 is higher than for any studied antibody previously found complexed with SARS-CoV-1. Based on physical chemical analysis and free energies estimates, we can shed some light on the involved molecular recognition processes, their clinical aspects, the implications for drug developments, and suggest structural modifications on the CR3022 antibody that would improve its binding affinities for SARS-CoV-2 and contribute to address the ongoing international health crisis.

Reversible serine proteinase inhibitors comprise 18 unrelated families. Each family has a distinct representative structure but contains a surface loop that adopts the same, canonical conformation in the enzyme–inhibitor complex. The Laskowski mechanism universally applies for the action of all canonical inhibitors independent of their scaffold, but it has two nontrivial extrapolations. Intrascaffolding additivity states that all enzyme-contacting loop residues act independently of each other, while interscaffolding additivity claims that these residues act independently of the scaffold. These theories have great importance for engineering proteinase inhibitors but have not been comprehensively challenged. Therefore, we tested the interscaffolding additivity theory by hard-randomizing all enzyme-contacting canonical loop positions of a Kazal- and a Pacifastin-scaffold inhibitor, displaying the variants on M13 phage, and selecting the libraries on trypsin and chymotrypsin. Directed evolution delivered different patterns on both scaffolds against both enzymes, which contradicts interscaffolding additivity. To quantitatively assess the extent of non-additivity, we measured the affinities of the optimal binding loop variants and their binding loop-swapped versions. While optimal variants have picomolar affinities, swapping the evolved loops results in up to 200,000-fold affinity loss. To decipher the underlying causes, we characterized the stability, overall structure and dynamics of the inhibitors with differential scanning calorimetry, circular dichroism and NMR spectroscopy and molecular dynamic simulations. These studies revealed that the foreign loop destabilizes the lower-stability Pacifastin scaffold, while the higher-stability Kazal scaffold distorts the foreign loop. Our findings disprove interscaffolding additivity and show that loop and scaffold form one integrated unit that needs to be coevolved to provide high-affinity inhibition.

Inhibitor of nuclear factor kappa B kinase subunit beta (IKK-β), a specific regulator of nuclear factor-κB (NF-κB), is considered a valid target to design novel candidate drugs to treat rheumatoid arthritis and various cancers. In the present study, quantitative structure–activity relationships (QSAR) and molecular docking techniques were used to screen for new IKK-β inhibitors from a series of 2-acylamino-3-aminothienopyridine analogs. During the two-dimensional QSAR phase, the statistical model partial least square was selected from among two alternatives (r2 = 0.868, q2 (cross-validation) = 0.630). Descriptors with positive or negative contributions were derived from the created model. To build of three-dimensional QSAR models, we used three different fingerprints as analysis precepts for molecular clustering and the subsequent division of training sets and test sets. The best model, which used fingerprint model definition language public keys, was selected for further prediction of the compounds’ activities. Favorable physicochemical, structural, electrostatic, and steric properties were derived from the created QSAR models and then used for drug design with an in-house library. Amongst the designed compounds, compounds B01 and B02 showed good predicted activities. Furthermore, after a selecting the protein structure and docking method, docking studies were carried out to reveal the detailed interactions between the ligands and the target protein. Binding affinity was measured and sorted using the value of “-CDOCKER_ENERGY”. The high -CDOCKER_ENERGY values of compounds B01 (41.6134 kcal/mol) and B02 (40.1366 kcal/mol) indicated their prominent docking affinities.

Binding of indoloquinolines with different aliphatic side chains to a parallel G-quadruplex derived from the MYC promoter sequence was characterized by optical and calorimetric measurements. ITC experiments performed at different temperatures enabled the determination of molar heat capacity changes upon quadruplex binding and a partitioning of the total binding free enthalpy into contributing terms with hydrophobic effects being major driving forces for all derivatives. Whereas affinities increase for indoloquinolines equipped with a long and positively charged side arm, the highest contribution of specific intermolecular interactions anticipated to impart enhanced specificity is found for a ligand with an uncharged ether aliphatic tail. Obtained thermodynamic signatures may considerably aid in the rational selection of ligand side chains for G-quadruplex binders with enhanced affinity or selectivity.

A wealth of knowledge exists concerning echinoid substrate preference in recent and post-Paleozoic environments, however, relatively little is known of the environmental distribution and paleoecology of echinoids during the Paleozoic. The Paleozoic echinoids encompass the vast majority of the echinoid stem group, and were generally rare, but often present in Carboniferous communities across a range of paleoenvironments. We analyzed substrate preference in stem group echinoids during the Carboniferous Period, utilizing a dataset of echinoid occurrences compiled from museum collections and the literature. We focused on preference for substrate lithology (carbonate vs. siliciclastic) and grain size (fine-grained vs. coarse-grained). Using three different quantitative metrics, we analyzed substrate preferences in five families of echinoids, the Palaechinidae, the Archaeocidaridae, the Proterocidaridae, the Lepidesthidae, and the Lepidocentridae. Broadly, we found that most families showed a preference for carbonate environments, however relative affinities varied amongst families. The palaechinids showed a strong relative affinity for carbonate environments and were relatively more tolerant of coarse-grained environments than other echinoids. The Archaeocidaridae showed the widest environmental tolerance of any clade, with a high tolerance for siliciclastic and coarse-grained substrates. The Proterocidaridae and Lepidesthidae tended to have a relative affinity for fine-grained substrates. These differential tolerances and affinities for particular environments may have controlled the varying macroevolutionary histories of these clades in the Late Paleozoic.

The complexation and transport/immobilization abilities of humic acids are the most important environmental qualities of these substances. Therefore, the study of these properties is important for understanding their role both in natural systems and in human-driven applications. This contribution is focused on the diffusion of metal ions (Co, Cu and Ni) studied by means of a diffusion couple, and their immobilization in humic hydrogels. It was found that the diffusion characteristics of metal ions are strongly affected by their reactivity and their initial concentrations. The concentration dependence of Cu diffusivity exhibited a different trend when compared to Co and Ni, which the result of the high affinity of Cu to humic acids. When a metal ion is first complexed by humic acids it is bound in an exchangeable mode, which can be transferred to a nonexchangeable one. Our results indicate that the dynamic equilibrium established in the diffusion process includes mainly Cu ions in an exchangeable mode as a result of their high affinity and the high amount of bound Cu. Their transformation of bound Cu ions in strong Cu-humic complexes is very slow. In contrast, Co and Ni have much lower affinities to humic acids, thus their diffusivities are less affected by their reaction with humic acids.

A theoretical and experimental DFT study of the vibrational, structural and quantum properties of annomontine ( 1 ) and N -hydroxyannomontine ( 2 ) alkaloids using the B3LYP exchange-correlation functional with 6-311G (2d, p) basis set is presented. The theoretical geometry optimization data of the two structures were compared with the X-ray data of (1) in the associated literature and a conformational study is presented for both molecules, providing a good comprehension of the conformational stability. In addition, natural bond orbitals (NBOs), HOMO-LUMO energy gap and mapped molecular electrostatic potential surface (MEPS) calculations were also performed at the same calculation approach. The calculated UV spectra agreed well with the measured experimental data, with transitions assigned. The comparative IR studies confirmed the intramolecular hydrogen bonds of the conformations and the intermolecular hydrogen bonds of dimeric forms and also revealed several characteristic vibrations for the structures. Molecular docking studies with DNA Topoisomerase II-DNA complex showed binding free energies of −11.5 and −10.6 kcal/mol for 2 and 1 respectively, while for amsacrine, used for the treatment of leukemia, and doxorubicin, used for the treatment of breast cancer, bladder cancer, Kaposi's sarcoma, and acute lymphocytic leukemia, the presented binding free energies values are −10.0 and −9.9 kcal/mol respectively, revealing good bind affinities of the tested alkaloids with the complex. In vitro cytotoxicity assay revealed an expressive antitumor activity of N -hydroxyannomontine against human hepatocellular carcinoma cell line HepG2.

A series of eight MIII (PrIII, SmIII, NdIII, EuIII, GdIII, YIII, ErIII, and YbIII) coordination complexes were assembled from the 5-bromonicotinic acid N-oxide ligand (Hbno) under similar method. Single-crystal X-ray diffraction shows that these complexes display 1-D or bimetallacyclic coordination motifs, respectively. These structural discrepancies may be attributed to the radii of MIII ions, as well as their diverse affinities to N-oxide group. Furthermore, these lower-dimensional coordinative arrays can be further extended via additional secondary interactions, such as H-bonding and aromatic stacking interactions. All samples have been characterized by elemental analyses, and powder X-ray diffraction techniques. In addition, the luminescence sensing ability of 4 was investigated in detail.

The use of the electron-capture detector, ECD, to measure molecular electron affinities and kinetic parameters for reactions of thermal electrons with molecules at atmospheric pressure separated by chromatography and the sensitive and selective quantitative analysis of certain classes molecules are reviewed. The evaluated ground state electron affinities of the main group elements and diatomic molecules from slightly positive, 0+, to 3.6 eV are summarized. The electron affinities of twenty-seven superoxide states determined from pulsed discharge ECD and other methods are used to calculate one dimensional potential energy curves in agreement with theory. Advances in literature searches have uncovered ECD data in dissertations and theses and in the Russian and Japanese literature. These data, unpublished radioactive and pulsed discharge ECD thermal data from the University of Houston laboratories are used to report and evaluate electron affinities. The accuracy and precision of ECD electron affinities of organic molecules are identified and tabulated so that they can be added to compilations. A procedure for calculating the temperature dependence of electron molecule reactions is presented using kinetic and thermodynamic data. These are used toselect the most appropriate equipment and conditions for ECD analyses and physical determinations.

The odontostomatids are among the least studied ciliates, possibly due to their small sizes, restriction to anaerobic environments and difficulty in culturing. Consequently, their phylogenetic affinities to other ciliate taxa are still poorly understood. In the present study, we analyzed newly obtained ribosomal gene sequences of the odontostomatids Discomorphella pedroeneasi and Saprodinium dentatum, together with sequences from the literature, including Epalxella antiquorum and a large assemblage of ciliate sequences representing the major recognized classes. The results show that D. pedroeneasi and S. dentatum form a deep-diverging branch related to metopid and clevelandellid armophoreans, corroborating the old literature. However E. antiquorum clustered with the morphologically discrepant plagiopylids, indicating that either the complex odontostomatid body architecture evolved convergently, or the positioning of E. antiquorum as a plagiopylid is artifactual. A new ciliate class, Odontostomatea n. cl., is proposed based on molecular analyses and comparative morphology of odontostomatids with related taxa.

Representatives of chrysidid wasps are described for the first time from inclusions in Late Cretaceous Burmese amber. Five new genera and new species are described and illustrated: †Auricleptes nebulosus gen. et sp. nov., †Azanichrum pilosum gen. et sp. nov., †Bohartiura glabrata gen. et sp. nov., †Burmasega ammirabilis gen. et sp. nov., and †Miracorium tetrafoveolatum gen. et sp. nov. We coded 49 morphological characters for species representing the subfamilies Amiseginae, Loboscelidiinae, Cleptinae and Chrysidinae. The cladistic analysis recovered the following relationships: Cleptinae + (†Auricleptes + (†Burmasega + (†Miracorium + ((Loboscelidiinae + Amiseginae) + ((†Azanichrum + †Bohartiura) + (†Palaeochrum Krombein + (extant Chrysidinae)))))). In light of the cladistic results, we discuss the implications of characters for the interpretation of phylogenetic relationships within the family, and explore the main morphological changes occurred during the diversification of the chrysidid wasps.

Proton affinities (PA) and gas phase basicities (GB) of epoxide and episulfide derivatives with 2–6 carbon atoms were computed at the B3LYP/6-311++G(d,p) level of theory. These simple derivatives did not undergo ring opening upon protonation and their PAs were lower than 880 kJ mol−1. The PAs of the episulfides were higher than those of the corresponding epoxides. By substitution of strong electron donating groups such as phosphazene and guanidine, we stimulated ring opening upon protonation. This strategy led in designing of compounds with exceptional superbasicity of oxygen and sulfur sites. The calculated PAs were in the range of 1000–1200 kJ mol−1.

A previously undescribed six residues long peptide His-Arg-Phe-Leu-Arg-His was identified and purified from the skin secretion of the amphibian Phyllomedusa centralis. A synthetic analogue carboxyamidated HRFLRH-NH2 showed structural changes induced by CO2 and metal ions in aqueous solution when analyzed by NMR. The present work reports NMR structures for the carboxyamidated hexapeptide in the presence CO2, Zn2+ and Cd2+, suggesting possible affinity regions on the polypeptide chain for each ligand. The NMR structures were optimized by DFT to identify probable biding sites of these species in the polypeptide structure. To our best knowledge, this is the first time that a putative CO2 binding site is described on a peptide structure obtained in aqueous conditions, at room temperature.

A new class of anion receptors was designed using N-boryl and N-beryllium pyrrole derivative and their anion affinities were assessed in gas phase. The mechanism of these anion receptors is basis on aromatization of the pyrrole ring upon interaction with an anion. The anion affinities of these compounds toward F−, Cl−, NO3−, and SO42− anions, computed at the B3LYP/6-311++G(d,p) level of theory, were in the range of 100–808 kJ·mol−1 indicating that these compounds are among the strongest anion receptors reported so far. Also, the anion receptors exhibit exceptional affinity toward SO42− so that they can be considered as selective SO42− receptors.

A few novel previously synthesized 2,5-disubstituted 1,3,4-oxadiazoles with cytotoxic activity (1–17) were subjected to combined docking/quantum mechanical studies against chemotherapeutic targets. Selected macromolecular targets were those that were previously known to be inhibited by 1,3,4-oxadiazoles. Within this work, favorable binding modes/affinities of the oxadiazoles toward validated cancer targets were elucidated. Some oxadiazole structures exhibited ΔGbs comparable to or stronger than crystallographic ligands that were previously demonstrated to inhibit such targets. On the basis of obtained results, a general structure activity/binding relationship (SAR/SBR) was developed and a few 2,5-disubstituted 1,3,4-oxadiazole structures were proposed and virtually validated as potential cytotoxic candidates. To get more insight into structure binding relationship of candidate molecules within best correlated targets, docked conformation of the best in silico in vitro correlated oxadiazole structure was analyzed in terms of intermolecular binding energy components by functional B3LYP in association with split valence basis set using polarization functions (Def2-SVP). We believe that such modeling studies may be complementary to our previous results on the synthesis and cytotoxicity assessment of novel 1,3,4-oxadiazole derivatives through extending the scope of privileged structures toward designing new potential anti-tumor compounds.

The pathological processes of Alzheimer's disease and type 2 diabetes mellitus have been demonstrated to be linked together. Both PDE9 inhibitors and PPARγ agonists such as rosiglitazone exhibited remarkable preclinical and clinical treatment effects for these two diseases. In this study, a series of PDE9 inhibitors combining the pharmacophore of rosiglitazone were discovered. All the compounds possessed remarkable affinities towards PDE9 and four of them have the IC50 values, Graphical abstract Both PDE9 inhibitors and PPARγ agonists such as rosiglitazone exhibited remarkable preclinical and clinical treatment effects for Alzheimer's disease and type 2 diabetes mellitus. A series of PDE9 inhibitors combining the pharmacophore of rosiglitazone were discovered. Four of them exhibited excellent inhibitory activity against PDE9A and low cell toxicity. The most effective compound 11a gave the IC50 of 1.0 nmol/L towards PDE9, which was significantly better than the reference compounds PF-04447943 and BAY 73-6691.fx1

A new scelionine genus Indiscelio Veenakumari, Popovici and Talamas is described from India with type species Indiscelio aulon Veenakumari, Popovici and Talamas. Both sexes are described and imaged. Affinities with morphologically similar genera are discussed.

A hologram quantitative structure–activity relationship (HQSAR) and topomer comparative molecular-field analysis (CoMFA) were performed on 51 molecules that belong to the azo dyes to determine their affinities to cellulose fiber. The best HQSAR model was obtained by using atoms. Hydrogen atoms as a fragment distinction and a fragment size of 3–6 showed a leave-one-out cross-validated correlation coefficient (q2LOO) of 0.849 and a non-cross-validated correlation coefficient (r2) of 0.927. The best topomer CoMFA model with steric and electrostatic field parameters based on three fragments gave satisfactory results (q2LOO = 0.821; r2 = 0.934). External predictions were made on a test set and compared with previously reported models. Topomer CoMFA steric, electrostatic, and HQSAR atomic contribution maps were generated to analyze the structural features of this data set that govern their affinity potency.

Ubiquitin chains regulate distinct signaling events through cooperative interactions with effector proteins and deubiquitinases. Measuring the strength of these interactions is often challenging; either large amounts of material are required or one of the binding partners must be labeled for detection. We sought to develop a label-free method for measuring binding of ubiquitin chains to the proteasome-associated deubiquitinase UCH37 and its binding partner RPN13. The method we describe here is based on a fluorescence polarization competition (FP(comp)) assay in which fluorescent monoubiquitin is competed off the UCH37•RPN13 complex by the addition of an unlabeled ubiquitin chains. We show that the UCH37•RPN13 complex displays higher affinity toward chains with more than two ubiquitin subunits. Removing the ubiquitin-binding PRU domain of RPN13 does not change affinities. These results suggest UCH37•RPN13 acts to selectively recruit proteins modified with long chains (>2 subunits) to the proteasome for degradation. We also demonstrate that the FP(comp) assay is suitable for high-throughput screening, which is important considering both UCH37 and RPN13 are potential targets for cancer therapy.

Tectonic affinities of accreted basalts provide constraints on mass transport in convergent boundaries, improving our understandings on the evolution of regional geology. In this study, nineteen accreted basalts from the southernmost tip of Taiwan Island, which is on the convergent boundary between the Eurasian and Philippine Sea Plates, were analyzed for element concentrations as well as Sr, Nd, Hf, and Pb isotope ratios to investigate their tectonic affinities. All the samples contain > 3% LOI, reflecting post-magmatic alteration. LOI and Nb variation diagrams together with comparisons to oceanic basalt compositions indicated that the concentrations of most major elements and Rb, Sr, and Ba were modified by post-magmatic processes to varying extents, while P2O5, REE and HFSE remained immobile. Although some samples show Pb loss, most samples have Pb concentrations not affected by post-magmatic processes. Isotope ratios of Pb, Nd and Hf, generally reflect the mantle source characteristics. The eNd–eHf relationship and trace element abundance ratios indicated that the LREE-depleted samples were mostly scraped off the subducting South China Sea floor, reflecting the volumetric dominance of N-MORB on ocean floors. The overriding Philippine Sea Plate contributed both N-MORB and E-MORB to the accretionary prism. The tectonic affinities of the LREE-enriched samples, however, could not be unambiguously determined for the large geochemical variability of OIB from both subducting and overlying slabs. Based on our results, it is proposed that the tectonic affinity of the basalts in an accretionary prism can indicate the subduction polarity of the associated convergent boundary, providing a constraint for regional geology evolution.

Herein, we explore the coordination behaviours of Schiff bases derived from constituents of essential oils (viz. cinnamaldehyde and cuminaldehyde) and aromatic amines (viz. 2-aminophenol and 4-aminoantipyrene) towards the facial tricarbonylrhenium(I) core. The resultant rhenium(I) compounds: (µ-X)2[Re(CO)3]2 {where X = 2-{[3-phenylprop-2-en-1-ylidene]amino}phenol (ciap) (for 1) or 2-{[4-(propan-2-yl)benzylidene]amino}phenol (cuap) (for 2), fac-[Re(CO)3(apy)Cl] (apy = 4-aminoantipyrene) (3) and fac-[Re(CO)3(cinap)Cl] (cinap = 1, 5-dimethyl-2-phenyl-4-{[3-phenylprop-2-en-1-ylidene]amino}-1,2-dihydro-3H-pyrazol-3-one) (4) were formed. The metal compounds were spectroscopically characterized and structural elucidations were confirmed by single crystal X-ray diffraction. DFT studies were utilized to rationalize the contrasting coordination behaviours of the structural analogues, 1,5-dimethyl-2-phenyl-4-{[4-(propan-2-yl)benzylidene]amino}-1,2-dihydro-3H-pyrazol-3-one (cumap) and cinap in the formation of 3 and 4, respectively. These metal compounds showed affinities towards Calf-Thymus DNA based on UV-Vis DNA binding titrations and molecular docking studies revealed that they are groove binders. In addition, gel electrophoresis experiments indicated that steric factors has an influence on the DNA cleavage activities of the mono- and dinuclear rhenium(I) compounds.

Even though phosphinate and its analogs are very important guests in nature, the artificial receptors which are capable of selective recognition of phosphinate are rare. Here, we report a series of acetate and phosphinate selective hosts (1, 2 and 3) which utilize amide N H and aliphatic C H groups as hydrogen bonding donors. In this series of receptors, even though the amide N H hydrogen bonding element was found to be the most significant, by varying the polarity of C H group, the magnitude of recognition could be modulated considerably. The affinities of host 3 against all the tested anion guests showed significantly higher affinities compared with those of hosts 1 and 2, and this could be attributed to the difference of C H group polarities among the receptors 1, 2 and 3. Cα-H hydrogen in host 3 is the most highly polarized by the charged pyridinium group. Therefore, it is the strongest host in this series of hosts. From the experiments shown here, we demonstrated the importance of C H hydrogen bonding element as a decisive modulating moiety for anionic recognition.

Four series of para or meta - substituted thiazolylbenzenesulfonamides bearing Cl substituents were designed, synthesized, and evaluated as inhibitors of all 12 catalytically active recombinant human carbonic anhydrase (CA) isoforms. Observed affinities were determined by the fluorescent thermal shift assay and the intrinsic affinities were calculated based on the fractions of binding-ready deprotonated sulfonamide and CA bearing protonated hydroxide bound to the catalytic Zn(II) in the active site. Several compounds exhibited selectivity towards CA IX, an anticancer target. Intrinsic affinities reached 30 pM, while the observed affinities - 70 nM. The structure-intrinsic affinity relationship map of the compounds showed the energetic contributions of the thiazole ring and its substituents.