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Comparison of the proteolytic susceptibilities of homologous L‐amino acid, D‐amino acid, and N‐substituted glycine peptide and peptoid oligomers
Author(s) -
Miller Susan M.,
Simon Reyna J.,
Ng Simon,
Zuckermann Ronald N.,
Kerr Janice M.,
Moos Walter H.
Publication year - 1995
Publication title -
drug development research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.582
H-Index - 60
eISSN - 1098-2299
pISSN - 0272-4391
DOI - 10.1002/ddr.430350105
Subject(s) - chemistry , trypsin , amino acid , peptide , papain , peptoid , glycine , stereochemistry , chymotrypsin , peptide sequence , enzyme , carboxypeptidase a , biochemistry , carboxypeptidase , gene
A series of homologous L‐amino acid, D‐amino acid, and both parallel and anti‐parallel (retro) sequence N‐substituted glycine peptide and peptoid oligomers were prepared and incubated with a series of enzymes representative of the major classes of proteases. Each respective L‐amino acid containing peptide sequence was readily cleaved by the appropriate enzyme, namely Ac‐L‐ala‐L‐leu‐L‐phe‐L‐ala‐L‐leu‐L‐arg‐NH 2 by chymotrypsin, Ac‐L‐ala‐L‐ala‐L‐ala‐L‐leu‐L‐phe‐L‐arg‐NH 2 by elastase, Ac‐L‐ala‐L‐phe‐L‐glu‐L‐leu‐L‐ala‐L‐ala‐NH 2 by papain, Z‐L‐ala‐L‐his‐L‐phe‐L‐phe‐L‐arg‐L‐leu‐NH 2 by pepsin, Ac‐L‐phe‐L‐ala‐L‐arg‐L‐ala‐L‐arg‐L‐asp‐NH 2 by trypsin, and Ac‐L‐ala‐L‐tyr‐Lala‐L‐phe‐OH for carboxypeptidase A. In contrast, equivalent D‐amino acid containing and N‐substituted glycine containing oligomers were cleaved minimally or not at all by the respective enzymes. The N‐substituted glycine peptoids represent a new class of combinatorial diversity for lead discovery with improved pharmaceutical characteristics relative to L‐amino acid containing peptides. © 1995 Wiley‐Liss, Inc.