Publication Details (including relevant citation information):
Aki, K. and Okamura, E. Sci. Rep. 6, 21594; doi:10.1038/srep21594 (2016).
Although L-amino acids were selected as main constituents of peptides and proteins during chemical evolution, D-aspartyl (Asp) residue is found in a variety of living tissues. In particular, D-b-Asp is thought to be stable than any other Asp isomers, and this could be a reason for gradual accumulation in abnormal proteins and peptides to modify their structures and functions. It is predicted that D-b-Asp shows high resistance to biomolecular reactions. For instance, less reactivity of D-b-Asp is expected to bond cleavage, although such information has not been provided yet. In this work, the spontaneous peptide bond cleavage was compared between Asp isomers, by applying real-time solution-state NMR to eye lens aA-crystallin 51–60 fragment, S51LFRTVLD58SG60 and aB-crystallin 61–67 analog, F61D62TGLSG67 consisting of L-a- and D-b-Asp 58 and 62, respectively. Kinetic analysis showed how tough the uncommon D-b-Asp residue was against the peptide bond cleavage as compared to natural L-a-Asp. Differences in pKa and conformation between L-a- and D-b-Asp side chains were plausible factors to determine reactivity of Asp isomers. The present study, for the first time, provides a rationale to explain less reactivity of D-b-Asp to allow abnormal accumulation.