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The role of thermally generated 3-aminopropionamide as an intermediate in acrylamide formation in the Maillard reaction has been well established. Herein, the effect of epicatechin on the conversion of 3-aminopropionamide into acrylamide under oxidative conditions was investigated at 160-220 °C. Epicatechin promoted acrylamide generation and 3-aminopropionamide degradation. The stable isotope-labeling technique combined with UHPLC-Orbitrap-MS/MS analysis showed adduct formation between 3-aminopropionamide and the oxidized B ring of epicatechin to form a Schiff base. This initially formed Schiff base could directly degrade to acrylamide, undergo reduction or dehydration to other intermediates, and subsequently generate acrylamide. Based on accurate mass analysis, five intermediates with intact or dehydrated C rings were tentatively identified. Furthermore, reaction pathways were proposed that were supported by the changes in the levels of adducts formed during heating. To the authors' knowledge, this study is the first to reveal pathways through which flavanols promoted the formation of acrylamide in Maillard reactions.

Delivery of active protein especially enzyme is one of the major therapeutic challenge. Replacing or substituted invalid/improper acting protein offer fast and effective treatment of disease. Herein, we describe the synthesis and properties of biotinylated peptidomimetics consisting of oxoacid-modified 2,3, L-diaminopropionic acid residues with guanidine groups on its side chains. Electrophoretic analysis showed that the obtained compounds interact with FITC-labeled streptavidin or a streptavidin-β-galactosidase hybrid in an efficient manner. Complexes formed by the abovementioned molecules are able to cross the cell membranes of cancer or healthy cells and show promising compatibility with live cells. Analysis of β-galactosidase activity inside the cells revealed surprisingly high levels of active enzyme in complex-treated cells compared to controls. This observation was confirmed by immunochemical studies in which the presence of β-galactosidase was detected in the membrane and vesicles of the cells., (© 2024. The Author(s).)

The analysis of dietary supplements is far less regulated than pharmaceuticals, leading to potential quality issues. Considering their positive effect, many athletes consume supplements containing L-histidine and β-alanine. A new microfluidic method for the determination of L-histidine and β-alanine in dietary supplement formulations has been developed. For the first time, capacitively coupled contactless conductivity detection was employed for the microchip electrophoresis of amino acids in real samples. A linear relationship between detector response and concentration was observed in the range of 10-100 µmol L -1 for L-histidine (R 2  = 0.9968) and β-alanine (R 2  = 0.9954), while achieved limits of detection (3 × S/N ratio) were 4.2 µmol L -1 and 5.2 µmol L -1 , respectively. The accuracy of the method was confirmed using recovery experiments as well as CE-UV-VIS and HPLC-UV-VIS techniques. The developed method allows unambiguous identification of amino acids in native form without chemical derivatization and with the possibility of simultaneous analysis of amino acids with metal cations., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH, DE part of Springer Nature.)

Successful delivery of plasmid DNA into the microbial cells is fundamental in recombinant DNA technology. Natural bacterial transformation is limited to only certain species due in part to the repulsive forces between negatively charged DNA and bacterial membranes. Most common method of DNA delivery into bacteria is artificial transformation through heat shock and electroporation. These methods require sophisticated instruments and tedious steps in preparation of competent cells. Transformation by conjugation is also not applicable to all plasmids. Nanoparticles have been used successfully in therapeutics for drug delivery into animal cells. They are starting to gain popularity in plant sciences as novel DNA nano carriers. Despite their promise as tool for DNA delivery, their use in microbial cell transformation has not been reported yet. Here we report the synthesis of carbon dots (CDs) from citric acid and β-alanine and their use in DNA delivery into E. coli cells. CDs were fabricated using microwave assisted synthesis. Plasmids carrying RFP reporter and ampicillin resistance genes were transferred to bacterial cells and further confirmed using polymerase chain reaction. Our findings indicate that CDs can be used successfully for delivery of foreign DNA of up to 10 kb into E. coli. We have demonstrated the use of β-alanine/citric acid carbon dots as nanocarriers of DNA into E. coli cells and identified their limitation in terms of the size of plasmid DNA they could carry. Use of these carbon dots is a novel method in foreign DNA delivery into bacterial cells and have a potential for the transformation of resistant organism for which there is still no reliable DNA delivery systems., (© 2021. The Author(s).)

With the recent explosion in high-resolution protein structures, one of the next frontiers in biology is elucidating the mechanisms by which conformational rearrangements in proteins are regulated to meet the needs of cells under changing conditions. Rigorously measuring protein energetics and dynamics requires the development of new methods that can resolve structural heterogeneity and conformational distributions. We have previously developed steady-state transition metal ion fluorescence resonance energy transfer (tmFRET) approaches using a fluorescent noncanonical amino acid donor (Anap) and transition metal ion acceptor to probe conformational rearrangements in soluble and membrane proteins. Here, we show that the fluorescent noncanonical amino acid Acd has superior photophysical properties that extend its utility as a donor for tmFRET. Using maltose-binding protein (MBP) expressed in mammalian cells as a model system, we show that Acd is comparable to Anap in steady-state tmFRET experiments and that its long, single-exponential lifetime is better suited for probing conformational distributions using time-resolved FRET. These experiments reveal differences in heterogeneity in the apo and holo conformational states of MBP and produce accurate quantification of the distributions among apo and holo conformational states at subsaturating maltose concentrations. Our new approach using Acd for time-resolved tmFRET sets the stage for measuring the energetics of conformational rearrangements in soluble and membrane proteins in near-native conditions., Competing Interests: WZ, BS, AN, MR, EE, YV, CJ, RM, EP, SG No competing interests declared, (© 2021, Zagotta et al.)

A facile solid-phase synthetic method for incorporating the imidazoline ring motif, a surrogate for a trans peptide bond, into bioactive peptides is reported. The example described is the synthesis of an imidazoline peptidomimetic analog of an insect pyrokinin neuropeptide via a cyclization reaction of an iminium salt generated from the preceding amino acid and 2,4-diaminopropanoic acid (Dap).

Cutaneous mast cells mediate numerous skin inflammatory processes and have anatomical and functional associations with sensory afferent neurons. We reveal that epidermal nerve endings from a subset of sensory nonpeptidergic neurons expressing MrgprD are reduced by the absence of Langerhans cells. Loss of epidermal innervation or ablation of MrgprD-expressing neurons increased expression of a mast cell gene module, including the activating receptor, Mrgprb2, resulting in increased mast cell degranulation and cutaneous inflammation in multiple disease models. Agonism of MrgprD-expressing neurons reduced expression of module genes and suppressed mast cell responses. MrgprD-expressing neurons released glutamate which was increased by MrgprD agonism. Inhibiting glutamate release or glutamate receptor binding yielded hyperresponsive mast cells with a genomic state similar to that in mice lacking MrgprD-expressing neurons. These data demonstrate that MrgprD-expressing neurons suppress mast cell hyperresponsiveness and skin inflammation via glutamate release, thereby revealing an unexpected neuroimmune mechanism maintaining cutaneous immune homeostasis., Competing Interests: Declaration of interests D.H.K. has a patent pending for the use of β-ala to suppress MC activation in disease states. The remaining authors declare no competing interests., (Copyright © 2021 Elsevier Inc. All rights reserved.)

The formation of peptide bonds by energetic processing of amino acids is an important step towards the formation of biologically relevant molecules. As amino acids are present in space, scenarios have been developed to identify the roots of life on Earth, either by processes occurring in outer space or on Earth itself. We study the formation of peptide bonds in single collisions of low-energy He 2+ ions (α-particles) with loosely bound clusters of β-alanine molecules at impact energies typical for solar wind. Experimental fragmentation mass spectra produced by collisions are compared with results of molecular dynamics simulations and an exhaustive exploration of potential energy surfaces. We show that peptide bonds are efficiently formed by water molecule emission, leading to the formation of up to tetrapeptide. The present results show that a plausible route to polypeptides formation in space is the collision of energetic ions with small clusters of amino acids.

The close synergy between peptides and nucleic acids in current biology is suggestive of a functional co-evolution between the two polymers. Here we show that cationic proto-peptides (depsipeptides and polyesters), either produced as mixtures from plausibly prebiotic dry-down reactions or synthetically prepared in pure form, can engage in direct interactions with RNA resulting in mutual stabilization. Cationic proto-peptides significantly increase the thermal stability of folded RNA structures. In turn, RNA increases the lifetime of a depsipeptide by >30-fold. Proto-peptides containing the proteinaceous amino acids Lys, Arg, or His adjacent to backbone ester bonds generally promote RNA duplex thermal stability to a greater magnitude than do analogous sequences containing non-proteinaceous residues. Our findings support a model in which tightly-intertwined biological dependencies of RNA and protein reflect a long co-evolutionary history that began with rudimentary, mutually-stabilizing interactions at early stages of polypeptide and nucleic acid co-existence.

Metal-Organic Frameworks (MOFs) are porous coordination networks assembled through metal complexes with organic linkers. Due to their chemical versatility, these materials are being investigated for various applications including gas storage and separation, biomedicine and catalysis. The aim of this work is the encapsulation of the model β-alanine amino-acid in the nanostructured zirconium-based MOF (UiO-66) which contains the ligand H 2 BDC (1,4-benzenedicaboxylic acid). Additionally, ligand functionalization (by using H 2 doBDC (2,5-dihydroxy-1,4-benzenedicarboxylic acid) and defect engineering have been carried out to produce UiO-66 derivatives, in order to modify the host-guest interactions, and hence study their influence on the β-alanine loading capacity and release kinetics. The as-obtained materials have been characterized by X-ray diffraction (XRD), X-ray thermo diffraction (TDX), infrared (IR) spectroscopy, thermogravimetric analysis-differential scanning calorimetry (TG-DSC) and elemental analysis (EA). Morphology of nanoscale MOFs has been explored by transition electron microscopy (TEM). Adsorption isotherms have been constructed, and the concentration of β-alanine in the post-adsorption solution (supernatant) has been quantified by high performance liquid chromatography coupled with mass spectroscopy (HPLC-MS) and EA. Adsorption capacity values indicate that the presence of hydroxyl groups at the organic linker H 2 doBDC enhances the host-guess affinity between the framework and the adsorbate β-alanine. The influence of defect engineering, on the adsorption however, is not that obvious. On the other hand, desorption experiments show similar behaviour for H 2 doBDC-based derivatives. An adsorption mechanism has been proposed consisting of a combination of host-guest interaction at low concentrations, and covalent anchoring/ligand displacement by β-alanine at the inorganic clusters., Competing Interests: Declaration of competing interest None of the author has conflicts of interest., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Enzyme design and engineering strategies rely almost exclusively on nature's alphabet of twenty canonical amino acids. Recent years have seen the emergence of powerful genetic code expansion methods that allow hundreds of structurally diverse amino acids to be installed into proteins in a site-selective manner. Here, we will highlight how the availability of an expanded alphabet of amino acids has opened new avenues in enzyme engineering research. Genetically encoded noncanonical amino acids have provided new tools to probe complex enzyme mechanisms, improve biocatalyst activity and stability, and most ambitiously to design enzymes with new catalytic mechanisms that would be difficult to access within the constraints of the genetic code. We anticipate that the studies highlighted in this article, coupled with the continuing advancements in genetic code expansion technology, will promote the widespread use of noncanonical amino acids in biocatalysis research in the coming years., Competing Interests: Conflict of interest statement Nothing declared., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

In diagnostic microbiology, culture media are widely used for detection of pathogenic bacteria. Such media employ various ingredients to optimize detection of specific pathogens such as chromogenic enzyme substrates and selective inhibitors to reduce the presence of commensal bacteria. Despite this, it is rarely possible to inhibit the growth of all commensal bacteria, and thus pathogens can be overgrown and remain undetected. One approach to attempt to remedy this is the use of "suicide substrates" that can target specific bacterial enzymes and selectively inhibit unwanted bacterial species. With the purpose of identifying novel selective inhibitors, six novel phosphonopeptide derivatives based on d/l-fosfalin and β-chloro-l-alanine were synthesized and tested on 19 different strains of clinically relevant bacteria. Several compounds show potential as useful selective agents that could be exploited in the recovery of several bacterial pathogens including Salmonella , Pseudomonas aeruginosa , and Listeria .

The traditional photodynamic therapy (PDT) using a photosensitizer and oxygen under light generates reactive oxygen species (ROS) to kill tumor cells. However, its treatment efficiency is limited by insufficient oxygen in tumor cells. Herein, β-alanine modified gadofullerene nanoparticles (GFNPs) were explored to disrupt tumor vasculatures assisted by light for potent melanoma treatment. As tumor vasculatures are oxygen-rich, the yields of photo-induced singlet oxygen (1O2) by GFNPs are not subjected to the hypoxemia of tumor tissues. Different from the small molecule photosensitizer Chlorin e6 (Ce6), GFNPs realize high-efficiency tumor vascular disruption under light observed by using the mice tumor vascular dorsal skin fold chamber (DSFC) model. The tumor vascular disruption efficiency of GFNPs is size-dependent, and the smallest one (hydration diameter of ca. 126 nm) is more efficient. Mechanistically, the high yields of photo-induced 1O2 by GFNPs can lead to the destruction of the tumor vascular endothelial adherent junction protein-VE cadherin and the decrease of tumor vascular endothelial cells-CD31 proteins, inducing rapid tumor necrosis. In conclusion, our work provides an insight into the design of well-sized nanoparticles to powerfully treat melanoma assisted by light, as well as greatly extending the applications of PDT for robust tumor therapy.

In the present study, a pyridoxal-5'-phosphate (PLP)-dependent L-aspartate-α-decarboxylase from Tribolium castaneum (TcPanD) was selected for protein engineering to efficiently produce β-alanine. A mutant Tc PanD-R98H/K305S with a 2.45-fold higher activity than the wide type was selected through error-prone PCR, site-saturation mutagenesis, and 96-well plate screening technologies. The characterization of purified enzyme TcPanD-R98H/K305S showed that the optimal cofactor PLP concentration, temperature, and pH were 0.04% ( m/v ), 50 °C, and 7.0, respectively. The 1mM of Na + , Ni 2+ , Co 2+ , K + , and Ca 2+ stimulated the activity of TcPanD-R98H/K305S, while only 5 mM of Ni 2+ and Na + could increase its activity. The kinetic analysis indicated that TcPanD-R98H/K305S had a higher substrate affinity and enzymatic reaction rate than the wild enzyme. A total of 267 g/L substrate l-aspartic acid was consumed and 170.5 g/L of β-alanine with a molar conversion of 95.5% was obtained under the optimal condition and 5-L reactor fermentation.

Natural deep eutectic solvents (NADES) are a type of ionic liquid (IL) or deep eutectic solvent (DES), the ingredients of which are exclusively natural products (non-toxic and environmentally friendly). Here, we explore the potential of NADES as an alternative to conventional organic solvents (e.g., aqueous methanol or ethanol) for the extraction of flavonoids from Scutellaria baicalensis stem bark to investigate their extractability depending on structural variation. Four NADES, each containing citric acid in combination with β-alanine, glucose, xylitol, or proline (at a molar ratio of 1:1), and a variable amount of water, were used to extract the flavonoid aglycones: baicalein ( 1 ), scutellarein ( 3 ), wogonin ( 5 ), and oroxylin A ( 7 ), and their glycosides, baicalin ( 2 ), scutellarin ( 4 ), wogonoside ( 6 ) and oroxyloside ( 8 ) from the powdered bark of S. baicalensis . The chemical profile and yield of the extracts were determined using HPTLC and HPLC. The extractability of individual flavonoids was found to be influenced by the concentration of water (20-60%, w/w) in the NADES. Among the tested flavonoids, the extraction yield of baicalein ( 1 ), scutellarein ( 3 ), wogonin ( 5 ), oroxylin A ( 7 ) with NADES was 2 to 6 times that of aqueous methanol. However, the amount of their corresponding glycosides (baicalin ( 2 ), wogonoside ( 6 ) and oroxyloside ( 8 )) extracted with NADES was only 1.5-1.8 times higher than with aqueous methanol. Interestingly, the more hydrophilic glycosides were less extracted than their corresponding aglycones despite the high hydrophilicity of the NADES. These results prove that NADES may be used for extraction of compounds with a wide range of hydrophilicity., Competing Interests: The authors declare no conflict of interest.

In a more synthetical approach to the study of ion-specific phenomena, four dipodal bis(guanidinium) siloxanes have been synthesized starting from glycine, β-alanine, γ-aminobutanoic acid, L-proline and 1,3-bis(3-aminopropyl)tetramethyldisiloxane. Together with their non-amide progenitor they were comparatively studied in regards to their interactions with nine different anions: sulphate, chromate, molybdate, benzoate, chloride, azide, nitrite, nitrate and thiocyanate. Their aqueous solubilities, form, 1 H NMR and FT-IR spectra were examined while searching for anion-specific interactions falling in- or outside of the Hofmeister series. We show that although the "chao-" and "kosmotropic" ions affect the properties of solutions in a predictable way, more selective cation-anion pairing is responsible for phase separation and crystallinity. As a prominent example, crystal structure of one of the benzoate salts was successfully obtained and reveals a synergy of hydrophobic packing, ionic and hydrogen bonding. Immobilized but still flexible siloxane bridges give rise to crystals described by P 4 2 /n space group and neatly segregated into hydro- and lipophilic sections.

Supramolecular gel material built from low-molecular-weight (LMW) gelators finds potential applications in various fields, especially in drug delivery, cell encapsulation and delivery, and tissue engineering. The majority of the LMW gelators in these applications are based on functionalized peptides/amino acids consisting of proteinogenic amino acids which are proteolytically unstable. Herein, we have developed a new LMW gelator containing non-proteinogenic amino acid namely 2,3-diaminopropionic acid (Dap), a key precursor in the synthesis of many antibiotics namely viomycin and capreomycin, by functionalizing with fluorenylmethoxycarbonyl at both amino terminals of Dap [Fm-Dap(Fm)]. Hydrogelation test at different pH indicates that Fm-Dap(Fm) can form a hydrogel in a wide range of pH (4.9 to 9.1) with minimum hydrogelation concentration depends on the pH. The mechanical strength and thermal stability of the Fm-Dap(Fm) hydrogel material are found to decrease with increasing pH (acidic > neural/physiological > basic). The thermal stability of Fm-Dap(Fm) hydrogels is pH-dependent and elicits high stability at acidic pH. Also, Fm-Dap(Fm) hydrogels exhibit strong thixotropic property where regelation (self-healing) occurs upon release of stress. Morphological analysis indicates the formation of fibrils, which are entangled to form three dimensional network structures. Several spectroscopic measurements provided evidence for the self-assembly of Fm-Dap(Fm) molecules through intermolecular aromatic π-π stacking and hydrogen bonding interactions during hydrogelation. Interestingly, Fm-Dap(Fm) not only exhibits hydrogel formation but also shows cell viability and enhanced cell proliferation at physiological pH (7.4). Further, Fm-Dap(Fm) forms a hydrogel upon co-incubation with vitamin B 12 and also exhibits release of vitamin B 12 over a period. The current study thus demonstrates the development of a new hydrogel material, based on LMW gelator containing the non-proteinogenic amino acid, which can elicit cell viability, enhanced cell proliferation, drug encapsulation, and drug release properties. Hence, Fm-Dap(Fm) hydrogel could be an ideal material for biomedical applications, especially in tissue engineering and drug delivery., (Copyright © 2019 Elsevier B.V. All rights reserved.)

In the study presented herein, we explore the ability of copper complexes with coordinated pyridine-2-carboxaldehyde (pyca) or 2-acetylpyridine (acepy) ligands to promote the addition of amines (Schiff condensation) and other nucleophiles such as alcohols (hemiacetal formation). Distinct reactivity patterns are observed: unlike pyca complexes, acepy copper complexes can promote self-aldol addition. The introduction of a flexible chain via Schiff condensation with β-alanine allows the possibility of chelate ring ring-opening processes mediated by pH. Further derivatization of the complex [CuCl(py-2-C(H)[double bond, length as m-dash]NCH2CH2COO)] is possible by replacing its chloride ligand with different pseudohalogens (N3-, NCO- and NCS-). In addition to the change in their magnetism, which correlates with their solid-state structures, more unexpected effects in their cytotoxicity and relaxitivities are observed, which determines their possibility to be used as MRI contrast agents. The replacement of a chloride by another pseudohalogen, although a simple strategy, can be used to critically change the cytotoxicity of the Schiff base copper(ii) complex and its selectivity towards specific cell lines.

Tripodal nonameric mannoside glycodendrimer 1 with carbohydrate tethered triazole linked with the TRIS-glycine-β-alanine dipeptidic aromatic centered core was synthesized. Glycodendrimer 1 demonstrated potential in vitro anti-leishmanial activity. The bio-activity data was substantiated with molecular modelling and docking studies of 1 with the three-dimensional protein structure of Leishmanolysin., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Endowment of pH responsivity to anticancer peptides is a promising approach to achieve better selectivity to cancer tissues. In this research, a template peptide was designed based on magainin 2, an antimicrobial peptide with anticancer activity, and a series of peptides were designed by replacing different numbers of lysine with the unnatural amino acid, 2,3diaminopropionic acid (Dap), which has a positive charge at weakly acidic pH in cancer tissues, but is neutral at physiological pH 7.4. These Dap-containing peptides are expected to interact more strongly with tumor cells than with normal cells because 1) weakly acidic conditions form in tumors, and 2) the membrane of tumor cells is more anionic than that of normal cells. Although all examined peptides showed potent cytotoxicities to multidrug-resistant cancer cells at a weakly acidic pH (ED 50 ≈5 μm), the toxicity decreased with an increase in the number of Dap at pH 7.4 (8 Dap residues resulted in ED 50 ≈60 μm). Furthermore, the introduction of Dap reduced cytotoxicity against normal cells. Thus, Dap led to significantly improved cancer targeting due to a pH-dependent charge shift. Fluorescence imaging and model membrane experiments supported this charge-shift model., (© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Numerous long-standing questions in origins-of-life research center on the history of biopolymers. For example, how and why did nature select the polypeptide backbone and proteinaceous side chains? Depsipeptides, containing both ester and amide linkages, have been proposed as ancestors of polypeptides. In this paper, we investigate cationic depsipeptides that form under mild dry-down reactions. We compare the oligomerization of various cationic amino acids, including the cationic proteinaceous amino acids (lysine, Lys; arginine, Arg; and histidine, His), along with nonproteinaceous analogs of Lys harboring fewer methylene groups in their side chains. These analogs, which have been discussed as potential prebiotic alternatives to Lys, are ornithine, 2,4-diaminobutyric acid, and 2,3-diaminopropionic acid (Orn, Dab, and Dpr). We observe that the proteinaceous amino acids condense more extensively than these nonproteinaceous amino acids. Orn and Dab readily cyclize into lactams, while Dab and Dpr condense less efficiently. Furthermore, the proteinaceous amino acids exhibit more selective oligomerization through their α-amines relative to their side-chain groups. This selectivity results in predominantly linear depsipeptides in which the amino acids are α-amine-linked, analogous to today's proteins. These results suggest a chemical basis for the selection of Lys, Arg, and His over other cationic amino acids for incorporation into proto-proteins on the early Earth. Given that electrostatics are key elements of protein-RNA and protein-DNA interactions in extant life, we hypothesize that cationic side chains incorporated into proto-peptides, as reported in this study, served in a variety of functions with ancestral nucleic acid polymers in the early stages of life., Competing Interests: The authors declare no conflict of interest., (Copyright © 2019 the Author(s). Published by PNAS.)

DMDP acetic acid [N-carboxymethyl-2,5-dideoxy-2,5-imino-D-mannitol] 5 from Stevia rebaudiana is the first isolated natural amino acid derived from iminosugars bearing an N-alkyl acid side chain; it is clear from GCMS studies that such derivatives with acetic and propionic acids are common in a broad range of plants including mulberry, Baphia, and English bluebells, but that they are very difficult to purify. Reaction of unprotected pyrrolidine iminosugars with aqueous glyoxal gives the corresponding N-acetic acids in very high yield; Michael addition of both pyrrolidine and piperidine iminosugars and that of polyhydroxylated prolines to tert-butyl acrylate give the corresponding N-propionic acids in which the amino group of β-alanine is incorporated into the heterocyclic ring. These easy syntheses allow the identification of this new class of amino acid in plant extracts and provide pure samples for biological evaluation. DMDP N-acetic and propionic acids are potent α-galactosidase inhibitors in contrast to potent β-galactosidase inhibition by DMDP.

Amino acids are the building blocks of proteins, and their detection in outer space thus has implications on the origin of life. They form a zwitterionic structure in aqueous environments while adopting a neutral configuration in the gas phase. We perform an experimental and computational study on the number of water molecules needed for zwitterion formation of β-alanine. Our density functional theory investigation reveals that a minimum of five water molecules are required to form and stabilize the zwitterion. A characteristic connecting water molecule located between the COO - and NH 3 + groups is found to enhance the stability. This water molecule is also involved in a characteristic infrared active vibration at ≈1560 cm -1 , which is slightly shifted with the number of surrounding water molecules and is located in a spectral region outside of water vibrations. A corresponding infrared signal is found in high-resolution experimental spectra of β-alanine and water in a solid para-hydrogen matrix.

β-alanine is the rate-limiting point for the endogenous synthesis of carnosine in skeletal muscle. Carnosine has a wide range of implications for health, normal function and exercise performance. Whilst the physiological relevance of carnosine to different tissues remains enigmatic, β-alanine administration is a useful strategy to investigate the physiological roles of carnosine in humans. Intravenous administration of β-alanine is an interesting approach to study carnosine metabolism. However, sterilisation is mandatory due to the nature of the administration route. We evaluated whether sterilising doses of gamma radiation damages the molecular structure and leads to the loss of functional characteristics of β-alanine. Pure β-alanine was sterilised by gamma radiation in sealed glass vials using a 60Co multipurpose irradiator at a dose rate of 8.5 kGy.hour-1 totalising 10, 20, 25 30 and 40 kGy. The molecular integrity was assessed by X-ray Diffraction and changes in content were determined by High Performance Liquid Chromatography (UV-HPLC) and Triple Quadrupole Mass Spectrometer (HPLC/MS-MS). Sterility assurance was evaluated by inoculation assay. To examine whether functional properties were preserved, β-alanine was infused in one participant, who rated the level of paraesthesia on the skin using a 0-3 scale. Urinary β-alanine was quantified before and 24-h following β-alanine infusion using HPLC-ESI+-MS/MS. Irradiation resulted in no change in the crystal structure of β-alanine, no degradation, and no new peaks were identified in the dose range assayed. The inoculation assay showed the absence of viable microorganisms in all β-alanine samples, including those that did not undergo irradiation. Intravenous infusion of β-alanine resulted in paraesthesia and it detected in the urine as per normal. We conclude that gamma radiation is a suitable technique for the sterilisation of β-alanine. It does not lead to degradation, damage to the β-alanine structure, content or loss of function within the evaluated irradiation conditions., Competing Interests: The authors have declared that no competing interests exist.

Access to vitamin B 5 [(R)-pantothenic acid] and both diastereoisomers of α-methyl-substituted vitamin B 5 [(R)- and (S)-3-((R)-2,4-dihydroxy-3,3-dimethylbutanamido)-2-methylpropanoic acid] was achieved using a modular three-step biocatalytic cascade involving 3-methylaspartate ammonia lyase (MAL), aspartate-α-decarboxylase (ADC), β-methylaspartate-α-decarboxylase (CrpG) or glutamate decarboxylase (GAD), and pantothenate synthetase (PS) enzymes. Starting from simple non-chiral dicarboxylic acids (either fumaric acid or mesaconic acid), vitamin B 5 and both diastereoisomers of α-methyl-substituted vitamin B 5 , which are valuable precursors for promising antimicrobials against Plasmodium falciparum and multidrug-resistant Staphylococcus aureus, can be generated in good yields (up to 70 %) and excellent enantiopurity (>99 % ee). This newly developed cascade process may be tailored and used for the biocatalytic production of various vitamin B 5 derivatives by modifying the pantoyl or β-alanine moiety., (© 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Despite the great efforts for tumor therapy in the last decades, currently chemotherapy induced toxicity remains a formidable problem for cancer patients, and it usually prohibits the cancer therapy from successful completion due to severe side effects. In general, the main side effects of chemotherapeutic agents are from the as-produced reactive oxygen species (ROS) that not only harm the tumor cells but also damage the patients' organs. Here we report the application of amino acid derivatives of fullerene (AADF) in the chemotherapy which strongly scavenge the excess ROS to protect the tested mice against the chemotherapy-induced hepatotoxicity and cardiotoxicity. Two amino acids, i.e., L-lysine and β-alanine were separately employed to chemically modify C 70 fullerene, and L-lysine derivative of fullerene (C 70 -Lys) exhibits superior radical scavenging activity to β-alanine derivative of C 70 (C 70 -Ala). As expected, C 70 -Lys show much better protective effect than C 70 -Ala against the chemotherapy injuries in vivo, which is verified by various histopathological, haematological examinations and antioxidative enzyme studies. Moreover, the L-glutathione level is increased and the cytochrome P-450 2E1 expression is inhibited. They are potentially developed as promising bodyguards for chemotherapy protection.

Escherichia coli can derive all essential metabolites and cofactors through a highly evolved metabolic system. Damage of pathways may affect cell growth and physiology, but the strategies by which damaged metabolic pathways can be circumvented remain intriguing. Here, we use a ΔpanD (encoding for aspartate 1-decarboxylase) strain of E. coli that is unable to produce the β-alanine required for CoA biosynthesis to demonstrate that metabolic systems can overcome pathway damage by extensively rerouting metabolic pathways and modifying existing enzymes for unnatural functions. Using directed cell evolution, rewiring and repurposing of uracil metabolism allowed formation of an alternative β-alanine biosynthetic pathway. After this pathway was deleted, a second was evolved that used a gain-of-function mutation on ornithine decarboxylase (SpeC) to alter reaction and substrate specificity toward an oxidative decarboxylation-deamination reaction. After deletion of both pathways, yet another independent pathway emerged using polyamine biosynthesis, demonstrating the vast capacity of metabolic repair.

3-Aminopropanamide (3-APA) is the direct precursor of acrylamide produced in the Maillard reaction between asparagine and reducing sugars. In this research, we found that 3-APA could reduce acrylamide by the formation of adducts between acrylamide and 3-APA via Michael addition. The effects of temperature, heating duration and 3-APA/acrylamide ratio on the reduction of acrylamide were investigated. Addition of 3-APA to acrylamide at a molar ratio of 5:3 at 160 °C for 20 min reduced acrylamide by up to 47.29%. The major adduct was identified as 3,3',3'-nitrilotris, and its cytotoxicity on Caco-2 cells was evaluated to be much lower than acrylamide. The viability of Caco-2 cells retained at 88.31% and 86.43% after incubation with 16 mM 3,3',3'-nitrilotris for 24 and 48 hr, respectively, while those incubated with the same concentration of acrylamide were 23.33% and 19.12%, respectively., Practical Application: The current study reported 3-APA could reduce acrylamide through the Micheal addition reaction between 3-APA and acrylamide. The adduct showed significantly reduced cytotoxicity compared to acrylamide. The research is critical in evaluation and control of food contaminants. The results brought new insights in the area of food safety, especially in the mechanism researches on formation and mitigation of endogenous contaminants in thermal-processed foods., (© 2018 Institute of Food Technologists®.)

Ghrelin is a small peptide hormone that undergoes a unique posttranslational modification, serine octanoylation, to play its physiological roles in processes including hunger signaling and glucose metabolism. Ghrelin O-acyltransferase (GOAT) catalyzes this posttranslational modification, which is essential for ghrelin to bind and activate its cognate GHS-R1a receptor. Inhibition of GOAT offers a potential avenue for modulating ghrelin signaling for therapeutic effect. Defining the molecular characteristics of ghrelin that lead to binding and recognition by GOAT will facilitate the development and optimization of GOAT inhibitors. We show that small peptide mimics of ghrelin substituted with 2,3-diaminopropanoic acid in place of the serine at the site of octanoylation act as submicromolar inhibitors of GOAT. Using these chemically modified analogs of desacyl ghrelin, we define key functional groups within the N-terminal sequence of ghrelin essential for binding to GOAT and determine GOAT's tolerance to backbone methylations and altered amino acid stereochemistry within ghrelin. Our study provides a structure-activity analysis of ghrelin binding to GOAT that expands upon activity-based investigations of ghrelin recognition and establishes a new class of potent substrate-mimetic GOAT inhibitors for further investigation and therapeutic interventions targeting ghrelin signaling., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Lathyrism is a disease caused by excessive consumption of grass pea, Lathyrus sativus especially under conditions of severe drought. Grass pea contains 3-N-oxalyl-L-2, 3-diaminopropanoic acid (β-ODAP) a putative neurotoxin which acts through excitatory mechanism causing Neurolathyrism. Due to awareness of the disease, availability of food and levels of consumption of L. sativus there is reduction in lathyrism cases where higher consumption of L. sativus is reported in India. The present study was undertaken with the objective to assess the current scenario of consumption of L. sativus, incidence of cases of lathyrism, β-ODAP, protein and amino acids content in L. sativus pulse collected from three districts (Bilaspur, Durg and Raipur) of Chattisgarh state. For this purpose, a total of 17,755 (13,129 rural and 4626 urban) individuals from 151 villages and 60 wards from urban area were covered for clinical examination. Out of total 5769 households (HHs) covered during the survey, 1602 HHs were cultivators, 1791 HHs non-cultivators and 2376 agricultural and other labourers. A one day 24-hour re-call diet survey was carried out in 5758 HHs (4549 rural and 1209 urban). A total of 360 split grass pea (SGP) samples were collected to estimate β-ODAP, protein and amino acids content. Results of the study revealed that an average consumption of SGP was 20.9 gm/CU/day in Bilaspur and no consumption was reported among urban population of Raipur. Only nine old cases of lathyrism were found during the study. The mean β-ODAP content in SGP was 0.63 ± 0.14, 0.65 ± 0.13 and 0.65 ± 0.14 gm/100 gm, whereas the protein content was 27.0 ± 2.39, 27.0 ± 1.99 and 26.7 ± 1.90 gm/100 gm in samples collected from Bilaspur, Durg and Raipur districts respectively. Arginine content was high in SGP and sulphur containing amino acids (cysteine and methionine) were less than other amino acids. In conclusion, the consumption of SGP was lower in these three districts with lower β-ODAP content than earlier reports, thus the lower prevalence of lathyrism in the districts surveyed., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

A one-pot method was developed for the preparation of a series of β-alanine standards of moderate size (2 to ≥12 residues) for studies concerning the prebiotic origins of peptides. The one-pot synthesis involved two sequential reactions: (1) dry-down self-condensation of β-alanine methyl ester, yielding β-alanine peptide methyl ester oligomers, and (2) subsequent hydrolysis of β-alanine peptide methyl ester oligomers, producing a series of β-alanine peptide standards. These standards were then spiked into a model prebiotic product mixture to confirm by HPLC the formation of β-alanine peptides under plausible reaction conditions. The simplicity of this approach suggests it can be used to prepare a variety of β-peptide standards for investigating differences between α- and β-peptides in the context of prebiotic chemistry.

Background: Nucleobase-bearing peptides and their interaction with DNA and RNA are an important topic in the development of therapeutic approaches. On one hand, they are highly effective for modulating the nucleic-acid-based biological processes. On the other hand, they permit to overcome some of the main factors limiting the therapeutic efficacy of natural oligonucleotides, such as their rapid degradation by nucleases., Methods and Results: This article describes the synthesis and characterization of a novel thymine-bearing nucleoamino acid based on the l-diaminopropionic acid (l-Dap) and its solid phase oligomerization to α-peptides (oligoDapT), characterized using mass spectrometry, spectroscopic techniques, and scanning electron microscopy (SEM) analysis. The interaction of the obtained nucleopeptide with DNA and RNA model systems as both single strands (dA 12 , rA 12 , and poly(rA)) and duplex structures (dA 12 /dT 12 and poly(rA)/poly(rU)) was investigated by means of circular dichroism (CD) and ultraviolet (UV) experiments. From the analysis of our data, a clear ability of the nucleopeptide to bind nucleic acids emerged, with oligoDapT being able to form stable complexes with both unpaired and double-stranded DNA and RNA. In particular, dramatic changes in the dA 12 /dT 12 and poly(rA)/poly(rU) structures were observed as a consequence of the nucleopeptide binding. CD titrations revealed that multiple peptide units bound all the examined nucleic acid targets, with T Ldap /A or T Ldap /A:T(U) ratios >4 in case of oligoDapT/DNA and ~2 in oligoDapT/RNA complexes., Conclusion: Our findings seem to indicate that Dap-based nucleopeptides are interesting nucleic acid binding-tools to be further explored with the aim to efficiently modulate DNA- and RNA-based biological processes., Competing Interests: Disclosure The authors report no conflicts of interest in this work.

Poly (3-hydroxypropionate) (P3HP), a new member of thermoplastic of family polyhydroxyalkanoates (PHAs), has excellent characteristics of biodegradability and biocompatibility. By now no reports can be found about wild-type bacteria that naturally synthesize P3HP, so the main way to produce P3HP is chemical and biological methods. Chemical method by adding high cost 3-HP monomers or their structural analogs as precursors, has the drawbacks of toxicity, low effectiveness and high cost. Biological method using engineered strain may utilize inexpensive and renewable carbon source to produce P3HP and has gradually become more and more popular. We systematically review here the biosynthesis of P3HP research progress. The advantages and disadvantages of biosynthesis pathways of glycerol pathway, malonyl-CoA pathway and β-alanine pathway were analyzed.

Periodontal disease consists of chronic gingival inflammation characterized by both degradation of the periodontal connective tissue and alveolar bone loss. Drug therapy is used as an auxiliary treatment method in severe chronic periodontitis, aggressive periodontitis, and periodontitis-associated systemic disease. Nal-P-113, a modified antimicrobial peptide, specifically replaces the histidine residues of P-113 with the bulky amino acid β -naphthylalanine, and our previous studies have verified that this novel peptide is not toxic to the human body within a certain concentration range. The objective of the present study was to evaluate the effect of Nal-P-113 on periodontal pathogens and periodontal status in clinical studies. In a split-mouth clinical trial, the pocket depth and bleeding index values tended to decrease in the experimental group compared with those in the control group. SEM results verified that Nal-P-113 restrained the maturation of plaque. Based on real-time polymerase chain reaction, the levels of Fusobacterium nucleatum , Streptococcus gordonii , Treponema denticola, and Porphyromonas gingivalis in subgingival plaque were decreased when the subjects were given Nal-P-113. Bacterial growth curve analysis and a biofilm susceptibility assay verified that Nal-P-113 at a concentration of 20  μ g/mL restrained the growth of S. gordonii , F. nucleatum, and P. gingivalis and biofilm formation. Therefore, Nal-P-113 effectively reduces periodontal pathogens and ameliorates periodontal status.

Oligopeptides containing 2,3-diaminopropionic acid (Dap) serve as a unique model to study conformational effects on the ionizability of a side-chain group. In this study, conformations of acetylated isomeric dipeptide ions containing alanine (Ala) and Dap, AlaDapH + and DapAlaH + , are studied by infrared multiple photon dissociation (IRMPD) spectroscopy and computation. The IRMPD spectra are characterized in detail by comparing them with theoretical IR spectra of a set of low-energy conformations calculated at the ωB97X-D/6-311+G(d) level of theory. The averaged IR spectra according to the Boltzmann distribution of the set of conformations have a good match to the IRMPD spectra. The characteristic amide I band of AlaDapH + appears to be downshifted compared to that of DapAlaH + . The relative positions of the amide band suggest a stronger hydrogen-bonding interaction between the charged side-chain amino group and the amide carbonyl groups in AlaDapH + than in DapAlaH + . The stronger hydrogen bonding in the former is likely due to a better alignment of the N-H and O═C bonds, which enables an effective sequestering of the positive charge at the amino group. The effect results in a higher proton affinity of acetylated dipeptides with the Dap residue at the C-terminus.

Taurine, one of the sulfur-containing amino acids, has several functions in vivo. It has been reported that taurine acts on γ-aminobutyric acid receptors as an agonist and to promote inhibitory neurotransmission. Milk, especially colostrum, contains taurine and it is known that milk taurine is essential for the normal development of offspring. β-Alanine is transported via a taurine transporter and a protein-assisted amino acid transporter, the same ones that transport taurine. The present study aimed to investigate whether the growth and behavior of offspring could be altered by modification of the taurine concentration in milk. Pregnant ICR mice were separated into 3 groups: 1) a control group, 2) a taurine group, and 3) a β-alanine group. During the lactation periods, dams were administered, respectively, with 0.9% saline (10 ml/kg, i.p.), taurine dissolved in 0.9% saline (43 mg/10 ml/kg, i.p.), or β-alanine dissolved in 0.9% saline (31 mg/10 ml/kg, i.p.). Interestingly, the taurine concentration in milk was significantly decreased by the administration of β-alanine, but not altered by the taurine treatment. The body weight of offspring was significantly lower in the β-alanine group. β-Alanine treatment caused a significant decline in taurine concentration in the brains of offspring, and it was negatively correlated with total distance traveled in the open field test at postnatal day 15. Thus, decreased taurine concentration in the brain induced hyperactivity in offspring. These results suggested that milk taurine may have important role of regulating the growth and behavior of offspring., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Purpose: Rho-associated protein kinase (ROCK) inhibitors lower intraocular pressure (IOP) by increasing aqueous outflow through the trabecular meshwork (TM). The preclinical characterization of netarsudil, a new ROCK/norepinephrine transporter (NET) inhibitor currently in clinical development, is presented herein., Methods: The kinase inhibitory activity of netarsudil was compared to its esterase metabolite, netarsudil-M1, and 3 other ROCK inhibitors using a commercially available kinase assay kit. Disruption of actin stress fibers was measured in primary porcine TM cells and disruption of focal adhesions in transformed human TM (HTM) cells. Induction of fibrosis markers after exposure to transforming growth factor-β2 (TGF-β2) was conducted in primary HTM cells. Ocular hypotensive activity and tolerability of topical formulations were evaluated in normotensive Dutch Belted rabbits and Formosan Rock monkeys. In vitro corneal metabolism assays were conducted using dog, pig, rabbit, monkey, and human corneas. In vivo ocular pharmacokinetics was studied in Dutch Belted rabbits., Results: Netarsudil inhibited kinases ROCK1 and ROCK2 with a K i of 1 nM each, disrupted actin stress fibers and focal adhesions in TM cells with IC 50 s of 79 and 16 nM, respectively, and blocked the profibrotic effects of TGF-β2 in HTM cells. Netarsudil produced large reductions in IOP in rabbits and monkeys that were sustained for at least 24 h after once daily dosing, with transient, mild hyperemia observed as the only adverse effect., Conclusion: Netarsudil is a novel ROCK/NET inhibitor with high potency in biochemical and cell-based assays, an ability to produce large and durable IOP reductions in animal models, and favorable pharmacokinetic and ocular tolerability profiles.

Minor-groove binding hairpin polyamides (PAs) bind specific DNA sequences. Synthetic modifications can improve PA-DNA binding affinity and include flexible modules, such as β-alanine (β) motifs to replace pyrroles (Py), and increasing compound charge using N-terminal cationic substituents. To better understand the variations in kinetics and affinities caused by these modifications on PA-DNA interactions, a comprehensive set of PAs with different numbers and positions of β and different types of N-cationic groups was systematically designed and synthesized to bind their cognate sequence, the λB motif. The λB motif is also a strong binding promoter site of the major groove targeting transcription factor PU.1. The PA binding affinities and kinetics were evaluated using a spectrum of powerful biophysical methods: thermal melting, biosensor surface plasmon resonance and circular dichroism. The results show that β inserts affect PA-DNA interactions in a number and position dependent manner. Specifically, a β replacement between two imidazole heterocycles (ImβIm) generally strengthens binding. In addition, N-terminal cationic groups can accelerate the association between PA and DNA, but the bulky size of TMG can cause steric hindrance and unfavourable repulsive electrostatic interactions in some PAs. The future design of stronger binding PA requires careful combination of βs and cationic substituents.

Aim: Anchoring folic acid (FA) with a biomimetic peptidic linker resistant to proteolytic degradation to act as a homing device on functionalized carbon nanotubes., Materials & Methods: Ethylenediamine was attached to oxidized multiwalled carbon nanotubes (MWNTs) using 4-(4,6-dimethoxy-[1,3,5]triazin-2-yl)-4-methylmorpholinium tetrafluoroborate. FA was coupled with 6-aminohexanoic acid and derivatives of β-alanine, affording four intermediates, which connected to the MWNTs via peptidic linkers of various lengths., Results: Biomimetic nanomaterials were produced with FA as a homing molecule. The structure and properties of the nanomaterials were analyzed, confirming the versatility of the peptides used as linkers., Conclusion: Conjugates of FA attached to MWNTs via peptide linkers prepared from β-alanine residues are resistant to proteolytic degradation. Viability in colon cancer cells and normal colonocytes confirmed their lack of cytotoxicity.

Side effects from targeted drugs remain a serious concern. One reason is the nonselective binding of a drug to unintended proteins such as its paralogs, which are highly homologous in sequences and have similar structures and drug-binding pockets. To identify targetable differences between paralogs, we analyzed two types (type-I and type-II) of functional divergence between two paralogs in the known target protein receptor family G-protein coupled receptors (GPCRs) at the amino acid level. Paralogous protein receptors in glucagon-like subfamily, glucagon receptor (GCGR) and glucagon-like peptide-1 receptor (GLP-1R), exhibit divergence in ligands and are clinically validated drug targets for type 2 diabetes. Our data showed that type-II amino acids were significantly enriched in the binding sites of antagonist MK-0893 to GCGR, which had a radical shift in physicochemical properties between GCGR and GLP-1R. We also examined the role of type-I amino acids between GCGR and GLP-1R. The divergent features between GCGR and GLP-1R paralogs may be helpful in their discrimination, thus enabling the identification of binding sites to reduce undesirable side effects and increase the target specificity of drugs., (Copyright © 2017 The Authors. Production and hosting by Elsevier B.V. All rights reserved.)

A new series of primary ammonium monocarboxylate (PAM) salts of a nonsteroidal anti-inflammatory drug (NSAID), namely, tolfenamic acid (TA), and its β-alanine derivatives were generated. Nearly 67 % of the salts in the series showed gelling abilities with various solvents, including water (biogenic solvent) and methyl salicylate (typically used for topical gel formulations). Gels were characterized by rheology, electron microscopy, and so forth. Structure-property correlations based on single-crystal and powder XRD data of several gelator and nongelator salts revealed intriguing insights. Studies (in vitro) on an aggressive human breast cancer cell line (MDA-MB-231) with the l-tyrosine methyl ester salt of TA (S7) revealed that the hydrogelator salt was more effective at killing cancer cells than the mother drug TA (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay); displayed better anti-inflammatory activity compared with that of TA (prostaglandin E 2 assay); could be internalized within the cancer cells, as revealed by fluorescence microscopy; and inhibited effectively migration of the cancer cells. Thus, the easily accessible ambidextrous gelator salt S7 can be used for two purposes: as an anti-inflammatory topical gel and as an anticancer agent., (© 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

We present a theoretical study of neutral clusters of β-alanine molecules in the gas phase, (β-ala) n n ≤ 5. Classical molecular dynamics simulations carried out with different internal excitation energies provide information on the clusters formation and their thermal decomposition limits. We also present an assessment study performed with different families of density functionals using the dimer, (β-ala) 2 , as a benchmark system. The M06-2X functional provides the best agreement in geometries and relative energies in comparison with the reference values computed with the MP2 and CCSD(T) methods. The structure, stability, dissociation energies and vertical ionization potentials of the studied clusters have been investigated using this functional in combination with the 6-311++G(d,p) basis set. An exhaustive analysis of intermolecular interactions is also presented. These results provide new insights into the stability, interaction nature and formation mechanisms of clusters of amino acids in the gas phase.

Experiments were performed to examine the effects of Maillard browning induced in the presence of metallic elements. The rate of brown pigment formation was shown to be reduced in model Maillard reactions performed in the presence of electropositive metals. Experiments involved reactions of d-xylose, d-arabinose and d-ribose with glycine, α-l- or β-alanine and l-valine in pH 7.0 phosphate buffer at ca. 100°C. "Browning" measured spectrophotometrically at 420nm was significantly lower (compared with controls) in selected reactions containing elemental Mg, Al, Mn and Sn particles. It was hypothesized that the metals acted in sacrificial anode redox fashion to reduce or eliminate dehydroreductones believed to be key Maillard intermediates ultimately leading to less browning., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

The synthesis of the radiolabeled glucagon receptor antagonist 1-[ 14 C] was accomplished based on decarboxylative iodination of acid 2 followed by "reattachment" of 14 C carboxylic function. The method allowed a significant reduction in the number of steps in preparation of the radiolabeled compound. Iodide 4, obtained by the halodecarboxylation, was converted to cyanide 5-[ 14 C], which was hydrolyzed to provide the radiolabeled acid 2-[ 14 C]. Coupling with β-alanine fragment and hydrolysis of ester 6-[ 14 C] completed the synthesis of the target molecule 1-[ 14 C]. The resulting compound was utilized in a mass balance and metabolism study where hepatic oxidation followed by a trace amount of sulfate conjugation and elimination was the main clearance pathway for 1 in humans., (Copyright © 2016 John Wiley & Sons, Ltd.)

The NAD-dependent malonate-semialdehyde dehydrogenase KES23460 from Pseudomonas sp. strain AAC makes up half of a bicistronic operon responsible for β-alanine catabolism to produce acetyl-CoA. The KES23460 protein has been heterologously expressed, purified and used to generate crystals suitable for X-ray diffraction studies. The crystals belonged to space group P2 1 2 1 2 1 and diffracted X-rays to beyond 3 Å resolution using the microfocus beamline of the Australian Synchrotron. The structure was solved using molecular replacement, with a monomer from PDB entry 4zz7 as the search model.

In this review, we demonstrate that the practical applications of a novel long-chain amidoamine derivative with a simple molecular structure (C18AA) are equivalent to or higher in number than those of supramolecules with complex molecular structures. Molecular assemblies of C18AA exhibit distinctive thermal responsiveness; namely, C18AA can form a gel with apolar organic solvents, while O/W emulsions of C18AA act as a heat-induced gelator that undergoes a phase transition from solution to gel upon heating. We also show that C18AA emulsions containing a quaternary ammonium salt develop an iridescent color over a specific temperature range. Further, molecular assemblies of C18AA serve as high-performance soft templates for the preparation of shape-controlled metal nanocrystals such as ultrathin Au nanowires and Pd nanowires.

Amidoamine derivative C18AA forms a highly viscous oil-in-water (O/W) emulsion, called an "emulsion gel." Previously, it was showed that the viscosity sensitively changes with the C18AA concentration, temperature, pH changes, and salt addition. In this work, C18AA concentration in the continuous aqueous phase ([C18AA] w ) was investigated at different compositions, and it was found that a threshold concentration value of 16.5 wt% was required to obtain a highly viscous emulsion gel below 45°C. C18AA formed micellar networks in the aqueous phase, and stimuli or additives increase the value of [C18AA] w , so that the C18AA micellar network could grow in the continuous aqueous phase.

LTX-401 is an oncolytic amino acid derivative with potential immunogenic properties. Here, we demonstrate that LTX-401 selectively destroys the structure of the Golgi apparatus, as determined by means of ultrastructural analyses and fluorescence microscopic observation of cells expressing Golgi-targeted GFP reporters. Subcellular fractionation followed by mass spectrometric detection revealed that LTX-401 selectively enriched in the Golgi rather than in mitochondria or in the cytosol. The Golgi-dissociating agent Brefeldin A (BFA) reduced cell killing by LTX-401 as it partially inhibited LTX-401-induced mitochondrial release of cytochrome c and the activation of BAX. The cytotoxic effect of LTX-401 was attenuated by the double knockout of BAX and BAK, as well as the mitophagy-enforced depletion of mitochondria, yet was refractory to caspase inhibition. LTX-401 induced all major hallmarks of immunogenic cell death detectable with biosensor cell lines including calreticulin exposure, ATP release, HMGB1 exodus and a type-1 interferon response. Moreover, LTX-401-treated tumors manifested a strong lymphoid infiltration. Altogether these results support the contention that LTX-401 can stimulate immunogenic cell death through a pathway in which Golgi-localized LTX-401 operates upstream of mitochondrial membrane permeabilization.