Aspartate racemization in synthetic peptides. Part 2. Tendency to racemization of aminosuccinyl residue

Abstract

Aminosuccinyl (Asu) peptides, containing a strained ring system, are very vulnerable to epimerization and, during their formation, even as transients, in the presence of nucleophilic and nonnucleophilic bases, partial epimerization occurs. In the presence of nucleophilic bases, Asu-peptides transform to a partially epimerized mixture of α- and β-aspartyl peptides, with the preponderance of the β- over the α-peptides. In the absence of any internal basic functionality such as the protonated guanidino group, chirally pure Asu-peptides could be synthesized by heating of β-benzyl-aspartyl [Asp(OBzl)] peptides in dimethylformamide to elevated temperatures or, from aspartyl (Asp) peptides having a free carboxy group, by the usual treatment with pentafluorophenol or 1-hydroxybenzotriazole-dicyclohexylcarbodiimide. However, in the presence of the strongly basic acetate ion and/or a guanidinium group the probability of aspartate racemization is increased.