Stereospecific Alkylation with Asymmetric Reagents

When undergoing nucleophilic reactions with proteins, α‐iodopropionic acid and its amide show greater specificity for SH groups than to inodoacetic acid and its amide. The kinetics and sterochemistry of the reactions of the D(+) and L(—) antiopodes of α‐iodopropionic acid and its amide with both eysteine and papain were investigated. The antipodes of the SH reagents reacted with these asymmetric SH compound at different rates. In the reaction with papain, the L(—) antipode of the acid reacted faster than the D(+) antipode; the stereochemical preference was inverted when the amide was used, the D(+)antipode reacting faster than the L(—)antipode. Arguing from the differing reactivities of the SH reagents and their antipodes and the pH dependence of the reaction rates, it has been suggested, that L(—)α iodopropionic acid is specifically oriented onto the reaction center through the concerted attractive and repulsive actios of a cations and an anionic group in the protein. These have been tentatively identifid as a protonated imidazole residue and a carboxylate group respectively. Parallels between these stereospecific alkylations and the catalytic action of the enzyme are discussed.