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The macrocyclic compounds mono- and bis-iron(II) clathrochelates were firstly studied as potential anti-fibrillogenic agents using fluorescent inhibitory assay, atomic force microscopy and flow cytometry. It is shown that presence of the clathrochelates leads to the change in kinetics of insulin fibrillization reaction and reduces the amount of formed fibrils (up to 70%). The nature of ribbed substituent could determine the activity of clathrochelates-the higher inhibitory effect is observed for compounds containing carboxybenzenesulfide groups, while the inhibitory properties only slightly depend on the size of complex species. The mono- and bis-clathrochelate derivatives of meta-mercaptobenzoic acid have close values of IC₅₀ namely 16 ± 2 and 24 ± 5 μM, respectively. The presence of clathrochelates decreases the fibril diameter from 5-12 nm for free insulin fibrils to 3-8 nm for these formed in the clathrochelate presence, it also prevents the lateral aggregation of mature fibrils and formation of superfibrillar clusters. However the addition of clathrochelate results in more heterogeneous (both by size and structure) insulin aggregates population as compared to the free insulin. This way, cage complexes-iron(II) clathrochelates are proposed as efficient agents able to suppress the protein aggregation processes., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Bis-pyridazine tectons support the structure of metallosupramolecular cavitand Cu2L4(4+), which is capable of selective encapsulation of SiF6(2-) anions by a set of multiple host-guest interactions.

A series of conjugates of peptide nucleic acids (PNA) and Zr(IV) complexes was prepared. Their ability to hydrolyze DNA was tested using MALDI-TOF mass spectrometry and HPLC. The most efficient artificial restriction enzyme found, PNA conjugate with Zr(IV) complex of tris(hydroxymethyl)-aminomethane, cleaves DNA targets sequence selectively in close proximity to the Zr(IV) complex. It was demonstrated that cleavage products are substrates of terminal transferase.

Peptide nucleic acids (PNAs) are neutral DNA analogues, which bind single-stranded DNA (ssDNA) strongly and with high sequence specificity. However, binding efficiency is dependent on the purine content of the PNA strand. This property make more difficult application of PNA as hybridization probes in, e.g., PNA chips, since at a set temperature the hybridization of a fraction of the DNA targets to the PNA probes does not obey Watson-Crick binding rules. The polypurine PNAs, for example, bind the mismatch containing DNA targets stronger, than the pyrimidine rich PNAs their fully complementary targets. Herein we show that PNA-DNA binding efficiency can be finely tuned by the conjugation of derivatives of naphthalene diimide (NADI) to the N-terminus of PNA using polyamide linkers of different lengths. This approach can potentially be used for the design of PNA probes, which bind their DNA targets with similar affinity independently of the PNA sequence.

A total of 16 oligodeoxyribonucleotides of general sequence 5'-TCTTCTZTCTTTCT-3', where Z denotes an N-acyl-N-(2-hydroxyethyl)glycine residue, were prepared via solid phase synthesis. The ability of these oligonucleotides to form triplexes with the duplex 5'-AGAAGATAGAAAGA-HEG-TCTTTCTATCTTCT-3', where HEG is a hexaethylene glycol linker, was tested. In these triplexes, an 'interrupting' T:A base pair faces the Z residue in the third strand. Among the acyl moieties of Z tested, an anthraquinone carboxylic acid residue linked via a glycinyl group gave the most stable triplex, whose UV melting point was 8.4 degrees C higher than that of the triplex with 5'-TCTTCTGTCTTTCT-3' as the third strand. The results from exploratory nuclease selection experiments suggest that a combinatorial search for strands capable of recognizing mixed sequences by triple helix formation is feasible.

Reported here are the results of a search for modified oligodeoxynucleotides with a 5'-terminal cytidine residue whose affinity for target strands is enhanced by 5'-acylamido groups. These acylamido groups were envisioned to act as molecular caps that bind to the exposed terminal base pair of the duplex with the target strand. A total of 52 capped oligonucleotides of the sequence R-CGGTTGAC, where R denotes the 5'-appendage and C a 5'-amino-2',5'-dideoxycytidine residue, were tested. Among the building blocks employed to modify the 5'-amino group of the DNA strand were carboxylic acid residues, either appended directly or via an amino acid residue, and aromatic aldehydes, coupled via reductive amination. The carboxylic acids employed ranged from Fmoc-glycine to (Fmoc)(2)-vancomycin and included a number of aromatic acids and bile acids. Small libraries were subjected to MALDI-monitored nuclease selection experiments, and selected compounds were tested in UV-melting assays with target strands. Cholic acid appendages stabilized terminal C:G base pairs to the greatest extent, with melting point increases of up to 10 degrees C. Further, the cholic acid residue enhanced base pairing fidelity at the terminus, as determined in melting analyses with target strands containing a mismatched nucleobase at the 3'-terminus.

[structure: see text]. Reported here is the synthesis of oligonucleotides containing a 2'-acylamido-2'-deoxyuridine residue at their 3'-terminus. Compared to control sequences bearing a thymidine residue, the quinolone-capped duplexes give higher UV melting points. In the case of (5'-ACGCGU-NA-2')2, where NA denotes a nalidixic acid residue, the melting point increase is up to 22 degrees C over that of (ACGCGT)2.

Oligodeoxynucleotides bearing 5'-appendages consisting of a nucleobase and an amide linkage were prepared from 5'-amino-5'-deoxyoligonucleotides, amino acid building blocks and thymine or uracil derivatives. Small chemical libraries of 5'-modified oligonucleotides bearing the nucleobase moieties via five, three or two atom linkages were subjected to spectrometrically monitored nuclease selections to identify members with high affinity for target strands. The smallest of the appendages tested, a uracil acetic acid substituent, was found to convey the greatest duplex stabilizing effect on the octamer 5'-T*GGTTGAC-3', where T* denotes the 5'-amino-5'-deoxythymidine residue. Compared to 5'-TTGGTTGAC-3', the modified sequence 5'-u-T*GGTTGAC-3' gives a duplex with 5'-GTCAACCAA-3' that melts 4 degrees C higher. The duplex-stabilizing effect of this 5'-substituent does not require a specific residue at the 3'-terminus of the complement and the available data suggest that the uracil moiety is located in the major groove of the duplex.

The synthesis and characterization of a series of meso-2-pyridylporphyrins and their Mg(2+) complexes are reported. Condensation of 4-alkylbenzyl-2,2'-dipyrromethanes (alkyl = Me, n-Pr, or n-Bu) with 2-pyridinecarboxaldehyde yielded a series of free-base meso-2-pyridylporphyrins. Insertion of Mg(2+) into the free-base porphyrins yielded the respective magnesium complexes. These compounds were characterized using 1D ((1)H and (13)C) and 2D ((1)H-(1)H COSY) NMR methods, UV-visible absorption spectroscopy, fluorescence spectroscopy, and mass spectrometry. The interplanar spacing of the dimers is sufficiently small that there is excitonic coupling of the constituent chromophores. The overall dissociation constant of these dimers is estimated at 2 x 10(-)(6) M. Addition of donor ligands such as acetone, DMF, DMSO, or pyridine converts the dimeric species to their respective constituent monomers. Titration of the dimeric complex with pyridine-d(5)() shows that disaggregation requires coordination of two pyridine molecules at independent binding sites. Tracking of the pyridine coordination by (1)H NMR spectroscopy allowed for determination of the equilibrium constant for the pyridine-induced disaggregation reaction (2.1 x 10(-)(3) M(2)). Both the spontaneous dissociation and the pyridine-induced disaggregation reactions occur by two steps.