Résumé de : BASAK (S), STEWART (NA), CHRETIEN (M) & BASAK (A) - 2004 - Aminoethyl benzenesulfonyl fluoride and its hexapeptide (Ac-VFRSLK) conjugate are both in vitro inhibitors of subtilisin kexin isozyme-1. FEBS Letters, 573 (1-3): pp. 186-194.

Using a number of intramolecularly quenched fluorogenic (IQF) substrates encompassing the subtilisin kexin isozyme-1 (SKI-1)-mediated cleavage sites of various viral glycoproteins, it is revealed that 4-12-Aminoethyl Benzenel SulfonylFluoride (AEBSF) can inhibit the proteolytic activity of SKI-1 mostly in a competitive manner. The measured IC50 values range from 200 to 800 nM depending on the nature of the substrate used. This is the first in vitro demonstration of a nonpeptide inhibitor of SKI-1. In an effort to enhance the selectivity and potency of SKI-1 inhibition, a hexapeptidyl derivative containing SKI-1 consensus sequence, Ac-Val-Phe-Arg-Ser-LeuLys-AEBSF, was prepared. The peptide sequence was derived from the primary auto-activation site of prodomain of SKI-1 itself terminating at Leu-Lys 138 and contains the crucial P4-basic and P2 alkyl side chain containing hydrophobic amino acids. Like AEBSF, the hexapeptidyl-AEBSF analog blocked SKI-1 cleavages of all IQF-subst! rates tested but with enhanced efficiency. (C) 2004 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.