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p ‐Azido‐L‐Phenylalanine Peptides. I: Synthesis of Peptide Ligands for Chymotrypsin and Aminopeptidases
Author(s) -
Escher Emanuel,
Jost Rolf,
Zuber Herbert,
Schwyzer Robert
Publication year - 1974
Publication title -
israel journal of chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.908
H-Index - 54
eISSN - 1869-5868
pISSN - 0021-2148
DOI - 10.1002/ijch.197400013
Subject(s) - chemistry , chymotrypsin , tripeptide , aminopeptidase , phenylalanine , stereochemistry , peptide , leucine , hydrolysis , dipeptide , thiazolidine , substrate (aquarium) , enzyme , amino acid , biochemistry , trypsin , oceanography , geology
p ‐Azido‐L‐phenylalanine peptides as ligands for α‐chymotrypsin and aminopeptidases were synthesized in two ways: (i) by direct incorporation of f‐butoxycarbonyl‐ p ‐azido‐L‐phenylalanine or its active esters, or (ii) by conversion of the nitro groups of the corresponding p ‐nitrophenylalanine‐containing peptides into azido functions. Both procedures yielded O‐ t ‐butylthreonyl‐ p ‐azidophenylalanylproline (L, L, L) which, like its parent tripeptide O‐ t ‐butylthreonyl‐phenylalanylproline (L, L, L), acted as a competitive inhibitor for leucine aminopeptidase (K i ≈ 7 to 8 × 10 −6 M). The two peptides p ‐azidophenylalanylphenylalanine (L, L) and p ‐azido‐phenylalanylphenylalanylproline (L, L, L) proved to be substrates for leucine aminopeptidase and for both aminopeptidases I and II from Bacillus stearothermophilus . Acetyl‐ p ‐azidophenylalanine ethyl ester (L) is a substrate of α‐chymotrypsin with K m ≈ 6 × 10 −4 M, closely resembling that of N‐acetyltyrosine ethyl ester (L), K m ≈ 5.4 × 10 −4 M, but with an approximately 100‐fold reduced maximum velocity of hydrolysis (V m ≈ 1.3 s −1 versus 211 s −1 ). The results obtained with photo‐affinity labelling will be described in a forthcoming paper.