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

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 A4 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 A4 hydrolase.

Graphical abstractDiphenyl ether and derivatives can either activate or inhibit the aminopeptidase activity of leukotriene A4 hydrolase, by binding at the hydrophobic pocket of LTA4H.Figure optionsDownload full-size imageDownload as PowerPoint slide