Title

Spontaneous cyclization of polypeptides with a penultimate Asp, Asn or isoAsp at the N-terminus and implications for cleavage by aminopeptidase

RIS ID

90998

Publication Details

Lyons, B., Kwan, A. H. & Truscott, R. (2014). Spontaneous cyclization of polypeptides with a penultimate Asp, Asn or isoAsp at the N-terminus and implications for cleavage by aminopeptidase. The Federation of European Biochemical Societies (FEBS) Journal, 281 (13), 2945-2955.

Abstract

A cyclic product that forms spontaneously from peptides that contain a penultimate Asp, Asn or isoAsp residue at the N-terminus has been characterized. This 2,5-diketopiperazine derivative forms under physiological conditions and is stable, showing little degradation even following heating at 60 °C. A mechanism for its formation from Asn and Asp peptides is proposed that involves a succinimide or isoaspartate intermediate. A diketopiperazine-modified peptide was also detected in human lens extracts. Since peptides that contain the diketopiperazine moiety are not readily hydrolysed by leucine aminopeptidase, it is hypothesized that proteins and peptides modified in this way in the body may not readily be digested by the normal proteolytic machinery of cells.

Grant Number

NMHRC/1008667

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