46] Acylation with dicarboxylic acid anhydrides

Abstract

This chapter discusses acylation with dicarboxylic acid anhydrides. Succinic and maleic anhydride, or analogs of these two compounds, is utilized in a variety of protein modification studies. During the course of the reaction most of the anhydride is hydrolyzed. The dicarboxylic acid side product may be separated from the modified protein by dialysis, by passage through a column of anion exchange resin (for example, Amberlite IRA-400 in the chloride form), or by gel exclusion chromatography (for example, with Sephadex G-25). The stability of the half amide adduct depends on the anhydride used in the reaction. Five purposes for which the dicarboxylic anhydrides have been utilized are discussed in the chapter, which include protein dissociation, protein hybridization, mapping of lysine peptides, peptide sequencing, lysine side-chain reactivity and function, and introduction of new functional groups. The relatively high specificity of succinic and maleic anhydride for primary amino groups suggests that these reagents may be useful for studying the reactivities of lysine side chains and for elucidating the roles these residues may play in the biological activities of proteins.