Low-molecular-weight aldehyde inhibitors of cathepsin G.
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.
Lesner
Adam
A
Faculty of Chemistry, University of Gdansk, 80-952 Gdansk, Poland. adas@chem.univ.gda.pl
Wysocka
Magdalena
M
Solek
Marta
M
Legowska
Anna
A
Rolka
Krzysztof
K
D000447:Aldehydes / Q000138:chemical synthesis / Q000494:pharmacology*; D056649:Cathepsin G; D002403:Cathepsins / Q000037:antagonists & inhibitors*; D055598:Chemical Phenomena; D009842:Oligopeptides / Q000138:chemical synthesis / Q000494:pharmacology*; D012697:Serine Endopeptidases
D000447:Aldehydes; D009842:Oligopeptides; D002403:Cathepsins; D012697:Serine Endopeptidases; D056649:Cathepsin G