Use of Merrifield solid phase peptide synthesis in investigations of biological deamidation of peptides and proteins

Merrifield solid phase peptide synthesis has been the principle research procedure used in the study of the chemistry and biological use of deamidation of asparaginyl and glutaminyl residues in peptides and proteins during the past 40 years. During the initial years of investigation, it permitted the qualitative demonstration that primary, secondary, and tertiary structure-determined deamidation half-times vary over a wide range under biological conditions and the discovery of two biological systems in which deamidations serve as molecular clocks. More recently, it has made possible such a thorough quantitative understanding of the structural dependence of deamidation that the deamidation rates of asparaginyl residues in proteins can be predicted from protein three-dimensional structures with a high degree of reliability. This, in turn, has led to the discovery that amide residues serve as molecular clocks in many biological systems and the demonstration of additional examples. In these investigations, Professor R. B. Merrifield contributed his techniques, time, and laboratory resources, both in personally teaching his methods to the principle investigators and in making available his laboratory in which more than 900 peptides were synthesized for this work.