20855-76-9Relevant articles and documents
Interaction of papain-like cysteine proteases with dipeptide-derived nitriles
L?ser, Reik,Schilling, Klaus,Dimmig, Elke,Gütschow, Michael
, p. 7688 - 7707 (2007/10/03)
A series of 44 dipeptide nitriles with various amino acids at the P 2 position and glycine nitrile at position P1 were prepared and evaluated as inhibitors of cysteine proteinases. With respect to the important contribution of the P2-S2 interaction to the formation of enzyme-inhibitor complexes, it was focused to introduce structural diversity into the P2 side chain. Nonproteinogenic amino acids were introduced, and systematic fluorine, bromine, and phenyl scans for phenylalanine in the P2 position were performed. Moreover, the N-terminal protection was varied. Kinetic investigations were carried out with cathepsin L, S, and K as well as papain. Changes in the backbone structure of the parent N-(tert-butoxycarbonyl)-phenylalanyl-glycine-nitrile (16), such as the introduction of an R-configured amino acid or an azaamino acid into P 2 as well as methylation of the P1 nitrogen, resulted in a drastic loss of affinity. Exemplarily, the cyano group of 16 was replaced by an aldehyde or methyl ketone function. Structure-activity relationships were discussed with respect to the substrate specificity of the target enzymes.
Thioesters of Amino Acid Derivatives as Thioacylating Agents in Thiopeptide Synthesis
Elmore, Donald T.,Guthrie, David J. S.,Kay, Gillian,Williams, Carrell H.
, p. 1051 - 1056 (2007/10/02)
Thioesters, mainly of N-substituted glycine, have been synthesized and examined for their ability to thioacylate amino acids, peptides, and esters and amides of amino acids and peptides.Methyl, ethyl, and benzyl thioesters have been obtained in high yield by thiohydrolysis of the corresponding imino esters.All were found to be excellent thioacylating agents for amino acids, though under the conditions used, they reacted much less readily with amino acid esters and amides including peptides, except where the reacting nucleophile was the amino group of Gly or the imino group of Pro.Attempts to improve the leaving properties of the alkoxy group (OR') in O-alkyl thioesters (RCSOR') by introduction of a 2-nitro substituent result in poorer yields of the thioester, probably because of competing elimination between the iminium group and OR' on treatment of the imino ester with H2S, although the nitro substituted thioesters are slightly more reactive than simple alkyl derivatives.The reaction of N-benzyloxycarbonylaminoacetonitrile with phenol gives a 30percent yield of a product which failed to yield any thioester on reaction with H2S.
Studies on hepatic agents. I. Synthesis of aminoacyl (and hydroxyacyl) aminoacetonitriles.
Suzue,Irikura
, p. 1417 - 1432 (2007/10/04)
-
