Preparation and Some Properties of Maleimido Acids and maleoyl derivatives of peptides

Abstract

N‐Alkoxycarbonylmaleimides 3 have been prepared and used to convert amino acids to maleimido acids (6–8) in aqueous solution. The carboxyl group of maleimido acids can be activated for amide or peptide synthesis (e.g., in the N‐succinimidyl esters 10); t‐butyl‐based protecting groups can be cleaved without damage to the maleimide moiety. Peptides carrying maleimide groups are accessible either from the maleimido acids (e.g., 11b, 15) or by direct maleoylation (e.g., 16b). The maleoyl group can be cleaved off by successive mild alkaline and acid hydrolysis or by hydrazinolysis. The reactivity of maleimides toward thiol groups suggests the use of maleimido acids and maleoylpeptides for preparing a wide range of conjugates of biochemical interest.