Racemization of an asparagine residue during peptide deamidation

Abstract

The Asn residue in the pentapeptide Asn-Gln-Asn-Glu-Gly undergoes racemization at the Calpha center in the course of deamidation of this residue through a succinimide intermediate. The succinimide intermediate is known to racemize at the corresponding center, leading to racemized products of deamidation. Return of this intermediate to reactant Asn is very unlikely in dilute solution where attack of product ammonia on the succinimide is precluded, and Asn racemization has not been previously observed. We give evidence that the observed racemization occurs at the tetrahedral-intermediate stage preceding the succinimide intermediate. The observation is significant for protein stability in vivo and in vitro and has importance in medicine, food chemistry, and archaeological/palaeological dating.