Potentiation of Chemical Reactivities at Protein Surfaces

Abstract

THE ability of toxicants which function as alkylating agents to react at specific sites on protein surfaces may be caused by differences in the reactivities of the functional groups of the side-chains as well as molecular geometry. Several mechanisms by which these reactivities might be modified are suggested by the results of some recent investigations on the kinetics of alkylation of amino-acids, peptides and proteins by the fungicide 2,4-dichloro-6-(o-chloro-anilino)-s-triazine¹. These studies show that only dissociated amino- and sulphydryl-groups can take part in the reactions, while the NH₃ ⁺ and SH groups are inert. In free amino-acids the latter groups predominate under physiological conditions, so that only small fractions of their potential reactivities are utilized. It is suggested that any structural features in protein molecules giving rise to micro-environments which behave as though they are more acidic or more basic than the surrounding medium can suppress or increase the ionization of the functional groups contained in them, thus giving rise to regions of low and high reactivity on the protein surface. It can be seen that the gains from such situations might be considerable when it is taken into account that only 0.25 per cent of the reaction potential of the amino-group of glycine is utilized at pH 7.0.