Citation

Zupan LA, Weiss RH, Hazen SL, Parnas BL, Aston KW, Lennon PJ, Getman DP, Gross RW. J. Med. Chem. 1993; 36(1): 95-100.

Copyright

(Copyright © 1993, American Chemical Society)

DOI

10.1021/jm00053a012

PMID

8421294

Abstract

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.

Language: en

Keywords

Animals; Dogs; Heart; Lactones; Myocardium; Phospholipases A; Phospholipases A2; Stereoisomerism; Structure-Activity Relationship