Substituted phosphonic analogues of phenylglycine as inhibitors of phenylalanine ammonia lyase from potatoes

Abstract

A series of phosphonic acid analogues of phenylglycine variously substituted in phenyl ring have been synthesized and evaluated for their inhibitory activity towards potato l-phenylalanine ammonia lyase. Most of the compounds appeared to act as moderate (micromolar) inhibitors of the enzyme. Analysis of their binding performed using molecular modeling have shown that they might be bound either in active site of the enzyme or in the non-physiologic site. The latter one is located in adjoining deep site nearby the to the entrance channel for substrate into active site.

Keywords: Aminophosphonates; Molecular modeling; PAL inhibitors; Structure-activity relationship.