Activation and inhibition of leukotriene A4 hydrolase aminopeptidase activity by diphenyl ether and derivatives

Xiaolu Jiang; Lu Zhou; Dengguo Wei; Hu Meng; Ying Liu; Luhua Lai

doi:10.1016/j.bmcl.2008.10.044

Activation and inhibition of leukotriene A4 hydrolase aminopeptidase activity by diphenyl ether and derivatives

Bioorg Med Chem Lett. 2008 Dec 15;18(24):6549-52. doi: 10.1016/j.bmcl.2008.10.044. Epub 2008 Oct 14.

Authors

Xiaolu Jiang¹, Lu Zhou, Dengguo Wei, Hu Meng, Ying Liu, Luhua Lai

Affiliation

¹ Beijing National Laboratory for Molecular Sciences, College of Chemistry and Molecular Engineering, Peking University, Beijing 100871, China.

PMID: 18952425
DOI: 10.1016/j.bmcl.2008.10.044

Abstract

The synthesis and biological evaluation of a series of diphenyl ether derivatives were described. The compounds can either activate or inhibit the aminopeptidase activity of leukotriene A(4) hydrolase, while at the same time do not influence the hydrolase activity. Further enzyme kinetics and molecular modeling investigation on these novel chemical activators revealed their possible activation mechanism. These compounds can be used as probes to regulate the aminopeptidase activity of leukotriene A(4) hydrolase.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Chemistry, Pharmaceutical
Drug Design
Enzyme Activation
Epoxide Hydrolases / antagonists & inhibitors*
Epoxide Hydrolases / chemistry*
Humans
Hydrolysis
Inhibitory Concentration 50
Kinetics
Models, Chemical
Models, Molecular
Molecular Conformation
Phenyl Ethers / chemistry*
Protein Binding
Substrate Specificity

Substances

Phenyl Ethers
phenyl ether
Epoxide Hydrolases
leukotriene A4 hydrolase