Abstract

Abstract 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.