ASPARTATE RACEMIZATION IN SYNTHETIC PEPTIDES .2. TENDENCY TO RACEMIZATION OF AMINOSUCCINYL RESIDUE

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 non-nucleophilic bases, partial epimerization occurs. In the presence of nucleophilic bases, Asu-peptides transform to a partially epimerized mixture of alpha- and beta-aspartyl peptides, with the preponderance of the beta- over the alpha-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 beta-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-hydroxy-benzotriazole-dicyclohexylcarbodiimide. However, in the presence of the strongly basic acetate ion and/or a guanidinium group the probability of aspartate racemization is increased.