%0 Journal Article
%T Structural determinants of haloenol lactone-mediated suicide inhibition of canine myocardial calcium-independent phospholipase A2
%J Journal of medicinal chemistry
%D 1993
%A Zupan, L. A.
%A Weiss, R. H.
%A Hazen, S. L.
%A Parnas, B. L.
%A Aston, K. W.
%A Lennon, P. J.
%A Getman, D. P.
%A Gross, R. W.
%V 36
%N 1
%P 95-100
%X Haloenol lactones are potent mechanism-based inhibitors of a novel class of calcium-independent phospholipases A2 which have been implicated as the enzymic mediators of membrane dysfunction during myocardial ischemia (Hazen, S. L.; et al. J. Biol. Chem. 1991, 266, 7227-7232). Herein we demonstrate that the ring size, hydrophobic group, and cryptic electrophile in the haloenol lactone moiety are important and modifiable determinants of the inhibitory potency of haloenol lactone-mediated inhibition of calcium-independent phospholipase A2. Direct comparisons between haloenol lactone-mediated inhibition of calcium-independent phospholipase A2 and the absence of inhibition with calcium-dependent phospholipase A2 further underscore the marked differences in the catalytic strategy employed by these two classes of intracellular phospholipases A2.<p /><p>Language: en</p>
%G en
%I American Chemical Society
%@ 0022-2623
%U http://dx.doi.org/10.1021/jm00053a012