Inhibition of human leukocyte elastase by phosphate esters of N-hydroxysuccinimide and its derivatives: direct observation of a phosphorylated enzyme by 31P nuclear magnetic resonance spectroscopy

No Thumbnail Available
Issue Date
1991-04-30
Authors
Groutas, William C.
Venkataraman, Radhika
Brubaker, Michael J.
Stanga, Michael A.
Advisor
Citation

Biochemistry. 1991 Apr 30; 30(17): 4132-6.

Abstract

A series of phosphate esters derived from N-hydroxysuccinimide and 3-alkyl-N-hydroxysuccinimide have been synthesized and found to be potent time-dependent irreversible inhibitors of human leukocyte elastase (HLE). The observed inhibitory activity in this series of compounds correlated well with the known preference of HLE for substrates with small hydrophobic side chains. Maximum potency was reached when a favorable aromatic interaction involving a phenyl group present in the inhibitor and an aromatic residue located in the vicinity of the S2' subsite was operative. 31P NMR spectroscopy was used to probe the mechanism of action of these compounds. Direct evidence is presented in support of a mechanism involving phosphorylation of the active site serine. These compounds constitute a new class of hydrolytically stable phosphorylating agents.

Table of Content
Description
Full text of this article is not available in SOAR.
publication.page.dc.relation.uri
DOI