Succinimide Formation from an NGR-Containing Cyclic Peptide: Computational Evidence for Catalytic Roles of Phosphate Buffer and the Arginine Side Chain.

ABSTRACT: The Asn-Gly-Arg (NGR) motif and its deamidation product isoAsp-Gly-Arg (isoDGR) have recently attracted considerable attention as tumor-targeting ligands. Because an NGR-containing peptide and the corresponding isoDGR-containing peptide target different receptors, the spontaneous NGR deamidation can be used in dual targeting strategies. It is well known that the Asn deamidation proceeds via a succinimide derivative. In the present study, we computationally investigated the mechanism of succinimide formation from a cyclic peptide, c[CH₂CO-NGRC]-NH₂, which has recently been shown to undergo rapid deamidation in a phosphate buffer. An H₂PO₄- ion was explicitly included in the calculations. We employed the density functional theory using the B3LYP functional. While geometry optimizations were

SUBMITTER: Kirikoshi R 

PROVIDER: S-EPMC5343963 | biostudies-literature | 2017 Feb

REPOSITORIES: biostudies-literature