Computational Studies on the Mechanisms of Nonenzymatic Intramolecular Cyclization of the Glutamine Residues Located at N-Termini Catalyzed by Inorganic Phosphate Species.

ABSTRACT: Glutamine (Gln) residues located at N-termini undergo spontaneous intramolecular cyclization, causing the formation of pyroglutamic acid (pGlu) residues. pGlu residues have been detected at the N-termini in various peptides and proteins. The formation of pGlu residues during the fermentation and purification processes of antibody drugs is one of the concerns in the design and formulation of these drugs and has been reported to proceed rapidly in a phosphate buffer. In this study, we have examined the phosphate-catalyzed mechanisms of the pGlu residue formation from N-terminal Gln residues via quantum chemical calculations using B3LYP density functional methods. Single-point energies were calculated using the second-order Møller-Plesset perturbation theory. We performed the calculations for

SUBMITTER: Nakayoshi T 

PROVIDER: S-EPMC7191561 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature