title: D-β-aspartyl residue exhibiting uncommon high resistance to spontaneous peptide bond cleavage.
abstract: 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-β-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-β-Asp shows high resistance to biomolecular reactions. For instance, less reactivity of D-β-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 αΑ-crystallin 51-60 fragment, S(51)LFRTVLD(58)SG(60) and αΒ-crystallin 61-67 analog, F(61)D(62)TGLSG(67) consisting of L-α- and D-β-Asp 58 and 62, respectively. Kinetic analysis showed how tough the uncommon D-β-Asp residue was against the peptide bond cleavage as compared to natural L-α-Asp. Differences in pKa and conformation between L-α- and D-β-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-β-Asp to allow abnormal accumulation.
authors.affiliation: Faculty of Pharmaceutical Sciences, Himeji Dokkyo University, 7-2-1 Kamiohno, Himeji 670-8524, Japan.
authors.forename: Kenzo
authors.initials: K
authors.lastname: Aki
authors.affiliation: Faculty of Pharmaceutical Sciences, Himeji Dokkyo University, 7-2-1 Kamiohno, Himeji 670-8524, Japan.
authors.forename: Emiko
authors.initials: E
authors.lastname: Okamura
mesh_terms: D026603:D-Aspartic Acid / Q000737:chemistry / Q000378:metabolism* / Q000493:pharmacokinetics; D006801:Humans; D026581:Isoaspartic Acid / Q000737:chemistry / Q000378:metabolism* / Q000493:pharmacokinetics; D007536:Isomerism; D007908:Lens, Crystalline / Q000737:chemistry; D019906:Nuclear Magnetic Resonance, Biomolecular; D059748:Proteolysis
chemical_list: D026581:Isoaspartic Acid; D026603:D-Aspartic Acid