Περίληψη:
A phosphonamide peptide,
N-(phenylethylphosphonyl)-Gly-L-Pro-L-aminohexanoic acid, previously
shown to block Clostridium histolyticum collagenases, was examined as a
putative inhibitor of endopeptidase 24.16 and endopeptidase 24.15.
Hydrolysis of two endopeptidase 24.16 substrates, i.e.
3-carboxy-7-methoxycoumarin (Mcc)-Pro-Leu-Gly-Pro-D-Lys-dinitrophenyl
(Dnp) and neurotensin, were completely and dose-dependently inhibited by
the phosphonamide inhibitor with K(I) values of 0.3 and 0.9 nM
respectively. In addition, the phosphonamide peptide inhibited the
hydrolysis of benzoyl (Bz)-Gly-Ala-Ala-Phe-(pAB) p-aminobenzoate and
neurotensin by endopeptidase 24.15 with about a 10-fold lower potency
(K(I) values of 5 and 7.5 nM respectively). The selectivity of this
inhibitor towards several exo- and endopeptidases belonging to the
zinc-containing metallopeptidase family established that a 1 muM
concentration of this inhibitor was unable to affect leucine
aminopeptidase, carboxypeptidase A, angiotensin-converting enzyme and
endopeptidase 24.11. The present paper therefore reports on the first
hydrophilic highly potent endopeptidase 24.16 inhibitor and describes
the most potent inhibitory agent directed towards endopeptidase 24.15
developed to date. These tools should allow one to assess the
contribution of endopeptidase 24.16 and endopeptidase 24.15 to the
physiological inactivation of neurotensin as well as other
neuropeptides.
Συγγραφείς:
BARELLI, H
DIVE, V
YIOTAKIS, A
VINCENT, JP
CHECLER, F
