Enzymatic strategies in chiral technologies

Professorial Chair Lecture

Guy Potter Benton Professorial Chair Lecture

Date

2-5-2001

Abstract

Reactions involving enzymes are in most cases stereospecific and the racemization that often appears in chemical synthesis is absent. This property led to the synthesis of single enantiomeric molecules as pharmaceuticals through two general strategies: asymmetric synthesis using prochiral reactants and kinetic resolution of racemic substrates. Enantiomeric drugs out in the market include antibiotics, hormones, anti-inflammatory, cardiovascular, central nervous system and anticancer preparations. A key step in this field is the identification and purification of enantioselective enzymes. Hydrolases are the most popular enzymes used, specifically lipases due to the non-requirement for expensive co-factors. Detection of these enzymes include titrimetric method and a qualitative method using agar plates containing the substrate and an indicator which forms a fluorescent complex with hydrolysis products. The purification of the enzyme is quite random and has to be established for each type which includes any or combination of the following: differential precipitation, gel filtration, ion exchange, affinity chromatography and hydrophobic interaction chromatography. The conversion of enzymes into "shelf reagents" which allow use of these catalysts under adverse conditions of pH, temperature and solvent system is one of the primary objectives. This can be attained through several immobilization techniques such as crosslinking, adsorption and entrapment. Some enantioselective lipases were identified from local microbial sources through a chemoenzymatic approach: synthesis of the ester of a racemic model aryl propionic acid, kinetic resolution of the racemic esters in the presence of microbial lipase and evaluation of the enzyme's enantioselectivity through HPLC analysis of the hydrolysates using a chiral column. Crosslinking experiments were carried out which facilitated the synthesis of an R-selective lipase.

Location

UPLB Main Library Special Collections Section (USCS)

Language

English

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