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Peptides containing Acylated C‐terminal Gem diamines: Novel Irreversible Inactivators of the Cysteine and Serine Proteinases †
Author(s) -
Gilmore B. F.,
Lynas J. F.,
Harriott P.,
Healy A.,
Walker B.
Publication year - 2006
Publication title -
chemical biology and drug design
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.59
H-Index - 77
eISSN - 1747-0285
pISSN - 1747-0277
DOI - 10.1111/j.1747-0285.2006.00390.x
Subject(s) - cysteine , chemistry , dipeptide , serine , stereochemistry , enzyme , cathepsin , oligopeptide , biochemistry , pancreatic elastase , acylation , cathepsin b , enzyme inhibitor , peptide , elastase , catalysis
This study reports on the synthesis of peptides containing C‐terminal acylated gem‐diamines and their utilization for the preparation of irreversible inactivators of the serine and cysteine proteinases. We have succeeded in obtaining an inhibitor Acetyl‐Val‐Pro‐ g ‐Val‐CO‐O‐C 6 H 4 ‐NO 2 of neutrophil and pancreatic elastases that functions in a time‐dependent manner, indicative of the action of an irreversible inactivator, functioning, most probably, through the formation of a long‐lived acyl enzyme intermediate. In addition, we have demonstrated the irreversible inhibition of the cysteine proteinase bovine cathepsin B, by chloroacetyl and bromoacetyl derivatives of a dipeptide gem‐diamine, Cbz‐Phe‐ g ‐Ala‐CO‐CH 2 Hal (Hal = Br, Cl).