Modeling the deamidation of asparagine residues via succinimide intermediates

Density functional theory (B3LYP/6-31G*) has been used to study the cycliza tion, deamidation and hydrolysis reactions of a model peptide. Single point energy calculations with the polarized continuum model drastically lower t he activation energy for cyclization in a basic medium. Confirmation of the experimental results that cyclization is slower than deamidation in acidic media and the opposite is true in basic media has enabled us to propose me chanisms for both processes.