PROBING THE SUBSTRATE-SPECIFICITY FOR LIPASES - A COMFA APPROACH FOR PREDICTING THE HYDROLYSIS RATES OF 2-ARYLPROPIONIC ESTERS CATALYZED BYCANDIDA-RUGOSA LIPASE

The enzyme catalyzed hydrolysis of esters 1-3, precursors of therapeut ically important non-steroidal antiinflammatory drugs, in the presence of the lipase from Candida rugosa was studied and the relative rates of the enzymatic hydrolysis were determined. With the exception of 3, which was not transformed under the reaction conditions, all transform ations proved to be highly enantiospecific. Usually the mechanism of e nantiorecognition is probed by substrate mapping. Although more theore tical approaches are existing, these all require knowledge of the thre e-dimensional structure of the enzyme. A model capable of correlating the extent of substrate hydrolysis as well as the initial reaction rat es with their stereoelectronic properties has been developed by a Comp arative Molecular Field Analysis (CoMFA) approach. This model does not require detailed knowledge of the three-dimensional structure of the enzyme and proved to be highly predictive. It is possible that this ki nd of approach holds promise for future work on enzyme-substrate inter actions.