d-β-aspartyl (Asp) residue has been found in a living body such as aged lens crystallin, although l-α-amino acids are constituents in natural proteins. Isomerization from l-α- to d-β-Asp probably modulates structures to affect biochemical reactions. At Asp residue, isomerization and peptide bond cleavage compete with each other. To gain insight into how fast each reaction proceeds, the analysis requires the consideration of both pathways simultaneously and independently. No information has been provided, however, about these competitive processes because each reaction has been studied separately. The contribution of Asp isomers to the respective pathways has still been veiled. In this work, the two competitive reactions, isomerization and spontaneous peptide bond cleavage at Asp residue, were simultaneously observed and compared in an αA-crystallin fragment, S51 LFRTVLD58 SG60 containing l-α- and d-β-Asp58 isomers. The kinetics showed that the formation of l- and d-succinimide (Suc) intermediate, as a first step of isomerization, was comparable at l-α- and d-β-Asp. Although l-Suc was converted to l-β-Asp, d-Suc was liable to return to the original d-β-Asp, the reverse reaction marked enough to consider d-β-Asp as apparently stable. d-β-Asp was also resistant to the peptide bond cleavage. Such apparent less reactivity is probably the reason for gradual and abnormal accumulation of d-β-Asp in a living body under physiological conditions. Copyright © 2016 European Peptide Society and John Wiley & Sons, Ltd.
Keywords: competitive reaction; d-β-aspartic acid; isomerization; kinetics; peptide bond cleavage; α-cystallin.
Copyright © 2016 European Peptide Society and John Wiley & Sons, Ltd.