Design, Synthesis and Testing of Transition State Analogues of Alanine Racemase as Antibacterials

Abstract

Transition state analogues have been designed for alanine racemase , an important enzyme target for the development of bacterial cell wall inhibitors. These analogues are based on the transition state structure obtained from MINDO/3 calculations on the reaction pathway of a model alanine racemization . A number of analogues have been synthesized and are shown to have weak anti-bacterial activity, but results from microbiological assays indicate that their antibacterial activity is not due to inhibition of alanine racemase . Subsequent n.m.r .studies have shown that they are unstable in aqueous environments. Formaldehyde has been identified as one of the degradation products, and the likely source of antibacterial activity.