Low-Molecular-Weight Aldehyde Inhibitors of Cathepsin G

Title: Low-Molecular-Weight Aldehyde Inhibitors of Cathepsin G

Volume: 16 Issue: 4

Author(s): Adam Lesner, Magdalena Wysocka, Marta Solek, Anna Legowska and Krzysztof Rolka

Affiliation:

Keywords: Cathepsin G, chymotrypsin, peptide aldehydes, peptidomimetics

Abstract: A series of aldehyde inhibitors with the general formula Ac-Phe-Val-Thr-X-CHO, where X = Lys, Arg, Phe, Tyr, p-nitro-L-phenylalanine (Nif), p-amino-L-phenylalanine (Amf), p-guanidine-L-phenylalanine (Gnf), pyridyl-L-alanine (Pal), was synthesized. The starting structure of this series based on our previous work on cathepsin G chromogenic substrates. The synthesis of all compounds was performed in solid phase applying Fmoc chemistry. We investigated the inhibitory potency of the obtained compounds against cathepsin G and bovine α-chymotrypsin and evaluated their dissociation constants (Ki). The studied peptides displayed different inhibition profiles and potency. As a result, a potent and selective inhibitor of cathepsin G with the sequence Ac-Phe-Val-Thr-Gnf-CHO, displaying Ki = 22 nM was obtained.

Cite this article as:

Lesner Adam, Wysocka Magdalena, Solek Marta, Legowska Anna and Rolka Krzysztof, Low-Molecular-Weight Aldehyde Inhibitors of Cathepsin G, Protein & Peptide Letters 2009; 16 (4) . https://dx.doi.org/10.2174/092986609787848144