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Research has been conducted on the racemic N-protected amino acids. The coupling of these acids with the amino components occurring via 2-chloro-4,6-dimethoxy-1,3,5-triazine in the presence of chiral tertiary amines has been investigated and the results indicate that the coupling proceeds enantioselectively.

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. [ABSTRACT FROM AUTHOR]

In this study, N-methylated analogs of hot-spots of insulin were designed and synthesized, in the expectation that they would inhibit the aggregation of both insulin hot-spots and the entire hormone. Synthesis of insulin "amyloidogenic" analogs containing N-methylated amino acid residues was performed by microwave-assisted solid phase according to the Fmoc/tert-Bu strategy. As a coupling reagent 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium toluene-4-sulfonate (DMT/NMM/TosO-) was used. Three independent methods were applied in aggregation studies of the complexes of insulin with its N-methylated peptides. Additionally, circular dichroism (CD) measurements were used to confirm that aggregation processes did not occur in the presence of the N-methylated analogs of hot-spot insulin fragments, and that insulin retains its native conformation. Of the seven N-methylated analogs of the A- and B-chain hot-spots of insulin, six inhibited insulin aggregation (peptides 1 and 3–7). All tested peptides were found to have a lower ability to inhibit the aggregation of insulin hot-spots compared to the capability to inhibit native hormone aggregation. [ABSTRACT FROM AUTHOR]

N-lipidated short peptides and amino acids immobilized on the cellulose were used as catalysts cleaved amide bonds under biomimetic conditions. In order to select catalytically most active derivatives a library of 156 N-lipidated amino acids, dipeptides and tripeptides immobilized on cellulose was obtained. The library was synthesized from serine, histidine and glutamic acid peptides N-acylated with heptanoic, octanoic, hexadecanoic and (E)-octadec-9-enoic acids. Catalytic efficiency was monitored by spectrophotometric determination of p-nitroaniline formed by the hydrolysis of a 0.1 M solution of Z-Leu-NP. The most active 8 structures contained tripeptide fragment with 1-3 serine residues. It has been found that incorporation of metal ions into catalytic pockets increase the activity of the synzymes. The structures of the 17 most active catalysts selected from the library of complexes obtained with Cu2+ ion varied from 16 derivatives complexed with Zn2+ ion. For all of them, a very high reaction rate during the preliminary phase of measurements was followed by a substantial slowdown after 1 h. The catalytic activity gradually diminished after subsequent re-use. HPLC analysis of amide bond splitting confirmed that substrate consumption proceeded in two stages. In the preliminary stage 24–40% of the substrate was rapidly hydrolysed followed by the substantially lower reaction rate. Nevertheless, using the most competent synzymes product of hydrolysis was formed with a yield of 60–83% after 48h under mild and strictly biomimetic conditions. [ABSTRACT FROM AUTHOR]

Reaction of 2-chloro-4,6-dimethoxy-1,3,5-triazine (CDMT) with bis-tetrafluoroborates of quinine and/or quinidine in the presence of sodium bicarbonate gave a pair of pseudo-enantiomeric coupling reagents: N,N'-bis-(4,6-dimethoxy-1,3,5-triazin-2-yl)quinine bis-tetrafluoroborate (2DMT/quinine/2BF4-) and N,N'-bis-(4,6- dimethoxy-1,3,5-triazin-2-yl)quinidine bis-tetrafluoroborate (2DMT/quinidine/2BF4-). The reagents activate the opposite enantiomers of racemic N-protected amino acids. By their reaction with two equivalents of racemic carboxylic components and diverse esters of amino acids, protected dipeptides were obtained with a predictable configuration and 95-99% enantiomeric homogeneity. [ABSTRACT FROM AUTHOR]

Quinine reacts with 2-chloro-4,6-dimethoxy-1,3,5-triazine (CDMT) via a multistage process leading to destruction of the quinuclidine fragment and attachment of two triazinyl substituents. In the first, reversible stage, CDMT reacts with the aromatic nitrogen of the quinoline, followed by the slow migration of triazine moiety on the bridgehead nitrogen atom of quinuclidine. The bicyclic system, after quaternization with CDMT, was opened by privileged attack of nucleophilic chloride on methylene carbon in the bridge substituted with vinyl group. In the final stage the second 4,6-dimethoxy-1,3,5-triazin-2-yl moiety was attached to the hydroxy group. The product structure was confirmed by X-ray crystallographic measurements, MS, 1H and 13C NMR, and IR spectroscopy. [ABSTRACT FROM AUTHOR]