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Low-molecular-weight aldehyde inhibitors of cathepsin G
Adam Lesner1, Magdalena Wysocka, Marta Solek
1Faculty of Chemistry, University of Gdansk, 80-952 Gdansk, Poland. adas@chem.univ.gda.pl
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 alpha-chymotrypsin and evaluated their dissociation constants (K(i)). 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 K(i) = 22 nM was obtained.
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