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Examples of Peptide–Peptoid Hybrid Serine Protease Inhibitors Based on the Trypsin Inhibitor SFTI‐1 with Complete Protease Resistance at the P1P1′ Reactive Site
Author(s) -
Stawikowski Maciej,
Stawikowska Roma,
Jaśkiewicz Anna,
Zabłotna Ewa,
Rolka Krzysztof
Publication year - 2005
Publication title -
chembiochem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.05
H-Index - 126
eISSN - 1439-7633
pISSN - 1439-4227
DOI - 10.1002/cbic.200400412
Subject(s) - peptoid , peptidomimetic , protease , chemistry , trypsin , peptide , serine protease , proteolysis , biochemistry , proteases , protease inhibitor (pharmacology) , glycine , chymotrypsin , enzyme , stereochemistry , amino acid , biology , antiretroviral therapy , viral load , immunology , human immunodeficiency virus (hiv)
Research in the field of protease inhibitors is focused on obtaining potent, specific and protease‐resistant inhibitors. To our knowledge, there are no reports in the literature that consider the application of N‐substituted glycine residues (peptoid monomers) for the design of peptidomimetic protease inhibitors. We hereby present the chemical synthesis and kinetic properties of two new analogues of the trypsin inhibitor SFTI‐1 modified at the P1 position. Substitution of Lys5 in SFTI‐1 by N ‐(4‐aminobutyl)‐glycine and N ‐benzylglycine, which mimic Lys and Phe, respectively, made these analogues completely protease‐resistant at their P1P1′ reactive sites. The analogues synthesised appeared to be potent inhibitors of bovine β‐trypsin and α‐chymotrypsin. These noncovalent, competitive and selective peptide–peptoid hybrid (peptomeric) inhibitors might open the way to targeting unwanted proteolysis.