First evidence of spontaneous deamidation of glutamine residue via cyclic imide to α- and γ-glutamic residue under physiological conditions

Abstract

At 37 "C and pH 7.4 the spontaneous deamidation of Gln-peptide proceeds prevalently via a glutarimide intermediate and gives a mixture of a-Glu-and y-Glu-peptide.

Structure‐dependent nonenzymatic deamidation of glutaminyl and asparaginyl pentapeptides

“…Deamidation of AcetylGlnGlyNHCH 3 in pH 7.4, 37 °C, 0.5 m phosphate buffer with ionic strength 0.5 has been reported (37) with rate constants determined for the glutarimide and hydrolysis mechanisms. These give deamidation half‐times of 430 days for the glutarimide and 1800 days for hydrolysis.…”

“…These give deamidation half‐times of 430 days for the glutarimide and 1800 days for hydrolysis. The combined deamidation half‐time is 350 days, with 82% proceeding via the glutarimide and 18% by hydrolysis (37).…”

Asymmetric glycosylation of soybean seed coat peroxidase

“…Glutamine residues also undergo deamidation, via a glutarimide intermediate, but at a much lower rate. 26 The products produced from the hydrolysis of the aspartyl succinimide are a-Asp and its isomer, b-Asp (isoaspartate) in the ratio of 1:3. 20 Racemization of the a-C of the cyclic imide occurs at a low rate, resulting in the formation of D D-Asp and D D-isoAsp after hydrolysis.…”

Glutamine deamidation of a recombinant monoclonal antibody

“…Direct hydrolysis is catalyzed by acid as well as base through the formation of a tetrahedral intermediate 3. At pH values of neutral and above, Gln deamidation may occur through the formation of a cyclic imide intermediate as proposed by Geiger and Clark,5 which was confirmed by Capasso et al .,6 by the direct observation of the cyclic imide intermediate and the products, α ‐ and γ ‐glutamate. Gln and Asn deamidation occurs through the same mechanisms, although Gln deamidation proceeds at a slower rate.…”