Amino acids coupling

Enzymes are highly specific catalysts in biological systems. They are proteins that consist of many amino acids coupled to each other by peptide bonds. The rather small enzyme insulin, for example, consists of 51 amino acids. The chain of amino... 

J Coste, E Frerot, P Jouin, B Castro. NCA A troublesome by-product in difficult amino acid coupling reactions, in CH Schneider, AN Eberle, eds. Peptides 1992. Proceedings of the 22nd European Peptide Symposium, Escom, Leiden 1993, pp 245-246. 

In humans the intronless gene encoding HR2 is located on chromosome 5. The human HR2 is a protein of 359 amino acids coupled to both adenylate cyclase and phosphoinositide second messenger systems by separate GTP-dependent mechanisms including Ga and also induces activation of c-Fos, c-Jun PKC and p70S6 kinase [16], Studies in different species and several human cells demonstrated that inhibition of characteristic features of the cells by primarily cAMP formation dominates in HR2-dependent effects of histamine. 

Lindlar s catalyst (5% Pd on CaC03, poisoned with Pb, 250 mg) and the mixture was hydrogenated at 0.2 MPa for 35 min at rt. TLC showed the conversion of azide [R/0.48 (CHCI /MeOH 10 1)] into amine (Rf 0.21), and showed evidence of O- to JV-acetyl migration, but no evidence of an anomeric mixture. The catalyst was filtered off and washed with MeOH, and removal of the solvent gave the amine as colorless oil. The crude oil was used immediately for amino acid coupling. 

Entry Carbonic Acid Derivative Parent Peptide or Amino Acid Coupling Conditions Product Yield (%) Ref... 

Two different synthetic approaches can be taken for the synthesis of peptide aldehydes using thiazolidine derivatives 1561 (1) formation of the aminothiazolidine precursor with subsequent amino acid coupling to afford the pseudopeptide, and (2) the synthesis of the peptide chain before synthesizing the thiazolidine precursor. Both approaches were successful in synthesizing peptide aldehydes with 90-95% yields and no epimerizationi56 ... 

Whobi = total amount of HOBt necessary for the whole library Fhobi = total volume of HOBt solution needed Fdic = volume of DIC required for each amino acid coupling reaction... 

Golebiowski et al. reported the solid-phase [92] and the solution-phase [93] syntheses of bycyclic diketopiperazines which were of great interest because their conformation was similar to the type-1 /i-turn motif. A Merrifield hydroxymethyl resin was esterified with a-N-Boc-fi-N-Fmoc-L-diaminopropionic acid and then mono-deprotected at the />-N with piperidine. Ugi-4CR of the resulting resin-bound amine gave the resin-bound adducts 168. Subsequent N-Boc deprotection and intramolecular N-alkylation afforded the ketopiperazines 169. The diketopiperazines 170 were formed via N-Boc amino acid coupling followed by N-Boc deprotection... 

Enzymatic Kinetic Resolution of N-Acyl Amino Acids Coupled with Racemization by N-Acyl Amino Acid Racemase Acylases are enzymes hydrolysing the N-acetyl derivatives of amino acids. They require the free carboxylate for activity and have long been used for the kinetic resolution of amino acids. The unreacted enantiomer is usually racemized in a separate step by treatment with acetic anhydride. While acylases from hog kidney have an L-specificity, bacterial acylases with L- and D-specificity of various origins have been isolated and used for the kinetic resolution of N-acetyl amino acids. An industrial process for the production of L-Met and other proteinogenic and non-proteinogenic L-amino acids such as L-Val, L-Phe, L-Norval, or L-aminobutyric acid has been established. Currently, several hundred tons per year of L-methionine are produced by this enzymatic conversion using an enzyme membrane reactor [46]. 

Scheme 13.18 The N-acylase-catalyzed kinetic resolution of N-acyl amino acids coupled with racemase induced racemization.

When N -deprotection reactions and amino acid coupling steps do not go to completion or proceed in low yields, repeated or prolonged reaction times should overcome these problems. Nevertheless, this is not always sufficient. The cause of this failure is thought to be self-association of the peptide chain by hydrogen bond formation leading to aggregation. This aggregation results in incomplete... 

Beginning in the late 1950s work in peptide synthesis was facilitated by the availabihty of protected amino acids, coupling agents, and pure solvents from commercial vendors. These chemical companies utilized chemistry mostly developed in academic laboratories. This synergism continues to the present and will be ongoing in the future as new peptide chemistry develops, especially for the building blocks necessary for combinatorial chenoistry. 

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