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Papain hydrolysis of X-phenyl-N-methanesulfonyl glycinates: A quantitative structure-activity relationship and molecular graphics analysis

1984; Elsevier BV; Volume: 229; Issue: 1 Linguagem: Inglês

10.1016/0003-9861(84)90136-x

1096-0384

Angelo Carotti, R. Nelson Smith, Shirlee Wong, Corwin Hansch, Jeffrey M. Blaney, Robert Langridge,

Enzyme Catalysis and Immobilization

The hydrolysis of 32 X-phenyl-N-methanesulfonyl glycinates by papain was investigated. It was found that the variation in the Michaelis constants could be rationalized by the following correlation equation: log1Km = 0.61π′3 + 0.46 MR4 + 0.55σ + 2.00 with a correlation coefficient of 0.945. In this expression, π′3 is the hydrophobic constant for the more lipophilic of the two possible meta substituents, MR4 is the molar refractivity of 4-substituents, and σ is the Hammett constant summed for all substituents. Using this equation, we designed, synthesized, and successfully predicted Km for a new congener intended to maximize binding (1Km). The interactions involved in enzyme-substrate binding, as characterized by the correlation equation, are interpreted using a computerconstructed color three-dimensional-graphics molecular model of the enzyme active site. The nonenzymatic hydrolysis (both acid and basic) of phenyl hippurates yield rate constants which are well correlated by Hammett equations; however, log k for both acid and alkaline hydrolysis are not linearly related to log1Kmor logkcatKm.