Claudio Chuaqui

Reactivity-selectivity correlations: I. The reactivity of alkyl aryl sulfates towards papain and ficin☆

Abstract A series of alkyl aryl sulfates has been investigated as inhibitors of papain and ficin activity. The results show that the percentage of residual enzymatic activity depends on several factors, including the solvolytic reactivity of the alkylating agent. It is possible to correlate the reactivities of the sulfates with a selectivity parameter which is based on product ratio results. The resulting correlations indicate that the reactivity-selectivity principle is applicable to this system. It is shown, however, from the results of amino acid analyses that specific methylation of active-site cysteine or histidine residues is not effective with the enzymes in the native or denatured state. This phenomenon contrasts with reported work on methyl p -nitrobenzenesulfonate in which extensive methylation of papain in the denatured state was observed. The finding that the nonspecific methylation of the enzymes by the alkyl aryl sulfates leads to inhibition of enzymic activity is discussed in terms of conformational and other effects.