Peptides s. a. Carboxylic acid

Peptides (s. a. Carboxylic acid amides, subst., Peptoids)... 

There has been a study of the mechanism of the activation of carboxylic acids to peptide formation by chloro-s -triazines in combination with tertiary amines. The first step, exemplified in Scheme 2 by the reaction of 2-chloro-4,6-disubstituted-l,3,5-triazines (18) with A -methylmorpholine, is formation of a quaternary triazinylammonium salt (20). Here there is NMR evidence for the formation at —50°C of the intermediate (19), showing that the substitution involves the two-step SnAt mechanism rather than a synchronous pathway. The subsequent reaction of (20) with a carboxylic acid yields the 2-acyloxy derivative (21), which carries an excellent leaving group for the amide-forming step. ... 

Hirano et al. [150, 151] immobilized several peptides, RGDS, on ethylene-acrylic acid copolymer (EAA, acrylic acid content 20 wt%) film by reacting the amino-terminal of the peptide with the carboxylic acid of the copolymer with the aid of a water-soluble carbodiimide, to form EAA-co-NH-RGDX. Their objective was to examine effect of the fourth residue, X, on the cell-attachment activity of the tetrapeptide, RGDX, where X is S, V and T. They also examined the activity of RGD, YIGSR and YIGSR-NH2 for comparison. The cell lines used were ovary CHO-K1 cell (Chinese hamster), kidney NRK cell... 

This synthesis also gives a small glimpse at the chemistry of heterocyclic compounds. Most active compounds in today s pharmaceuticals or agrochemicals include heterocycles, as well as most vitamins and natural products. The chemistry of heterocycles is thus very important and lectures or textbooks should be consulted.6 Formation of amide bonds also plays a large role in this problem. It was demonstrated that the strong amide bond can be formed from an amine and a carboxylic acid only after the acid has been activated. This can be done by transformation into the carboxylic halide or imidazolide or by application of an activating agent developed for peptide synthesis. 

Finally, other reactions can be performed directly using water as a solvent. Ugi s four components reaction, for example, provides an expedient access to peptidic scaffolds starting from an isocyanide, an amine, an aldehyde and a carboxylic acid. However, in competition to Ugi s reaction, Passerini ester formation often pollutes the reaction mixture and it is of great interest to perform this type of highly complex transformation in supported versions. Indeed, when an ammonium chloride supported aldehyde, similar to those used in Grieco s multicomponent reactions, are dissolved in water in the presence of an amine, the imine formation occurs within 15 min and isocyanide and acid can subsequently be added to the mixture. After 24 h at room temperature, amides were isolated in high yield with no other purification than washing with diethyl ether [135] (Fig. 44). 

The interactions of 8-lactams with PBPs indicate that these compounds are structural analogues of R-D-alanyl-D-alanine, the natural substrate of peptidoglycan transpeptidases and D-alanine carboxypeptidases, where R is the remainder of the pentapeptide. The mechanisms of the transpeptidase and carboxypeptidase reactions are thought to involve formation of an acyl-enzyme intermediate that can react with either a primary amine (e.g., an a-amino group) to form a peptide bond, or with water to form a carboxylic acid. In both reactions D-alanine is released before the acyl enzyme is formed. When a S-lactam antibiotic enters the binding site, the /1-lactam bond is hydrolyzed, and the resulting acyl group reacts with the active-site... 

Hydrolysis of a side-chain amide on a pol5q>eptide s glutamine or asparagine residues can yield a carboxylic acid. The process, called deamidation, is facilitated by elevated temperature and pH, resulting in loss of activity. The peptide... 

In the very first application of the tetrazole-based cycloaddition chemistry to proteins [39], a carboxylic acid functionalized tetrazole was coupled to a tripeptide (RGG) and the kinetics of the cycloaddition reaction between the tetrazole-modilied peptide and acrylamide was investigated under the 302-nm photoirradiation condition. The photolysis of the tetrazole-modilied peptide to its corresponding nitrile imine was extremely rapid with a first-order rate constant to be 0.14 s the subsequent cycloaddition with acrylamide proceeded with a second-order rate constant, 2, of 11.0 s . In the next step, the surface Lys residues of lysozyme... 

IsHii, S. Ion-exchange chromatography of amino acids and peptides. I. A new determination method of basic amino acids on a carboxylic acid resin. J. Biochem. (Tokyo) 43, 531—537 (1956). 

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