3D-QUANTITATIVE STRUCTURE-ACTIVITY-RELATIONSHIPS FOR HYDROPHOBIC INTERACTIONS - COMPARATIVE MOLECULAR-FIELD ANALYSIS (COMFA) INCLUDING MOLECULAR LIPOPHILICITY POTENTIALS AS APPLIED TO THE GLYCINE CONJUGATION OF AROMATIC AS WELL AS ALIPHATIC CARBOXYLIC-ACIDS

Hydrophobic interactions sometimes play an important role in enzymatic reactions. Tn order to interpret such reaction data on the basis of c omparative molecular field analysis (CoMFA) some method of introducing lipophilic parameters is necessary, since in the conventional CoMFA a pproach only electrostatic and steric fields are included in the origi nal version. In the present study, the idea of Molecular Lipophilicity Potential (MLP) was introduced into the original CoMFA algorithm and the glycine conjugation reactions were analyzed. The conjugation data used were the whole reaction of glycine conjugation as well as the ini tial step of the reaction where substrates bind to coenzyme CoA. The s ubstrates used include aromatic as well as aliphatic carboxylic acids. The CoMFA approach can explain data of aromatic and aliphatic carboxy lic acids with a single model, whereas the multiple linear regression (MLR) analysis affords separated results for these two kinds of carbox ylic acids. Thus, wide applicability of the CoMFA approach is supporte d and the aromatic and aliphatic carboxylic acids are suggested to beh ave in a common fashion in the conjugation reaction of the first proce ss.