EXPLORING THE HEXOKINASE GLUCOSE BINDING-SITE THROUGH CORRELATION-ANALYSIS AND MOLECULAR MODELING OF GLUCOSAMINE INHIBITORS

A series of N-substituted glucosamines has been designed. synthesized, and tested as inhibitors of yeast hexokinase. All derivatives exhibit ed competitive inhibition kinetics with respect to glucose. Quantitati ve structure-activity relationships were derived from the resulting in hibition data. The most significant equation demonstrated the existenc e of highly specific steric effects for the seven meta-substituted ben zoylglucosamines included in the relationship. Molecular modeling of p otential complexes between the inhibitors and the hexokinase substrate binding site strongly suggests that the steric effects arise from pot ential contacts with two amino acid residues lying in the region occup ied by the amide substituents.