Conformation-Dependent Racemization of Aspartyl Residues in Peptides

Abstract : Biologically uncommon D-aspartyl (D-Asp) residues have been detected in proteins of various tissues of elderly humans. The presence of D-Asp has been explained as a result of the racemization of L-Asp (denoted as Asp) in the protein of inert tissues. We have previously suggested that the racemization of Asp may depend on the conformation of the peptide chain. However, the nature of the peptide conformation that affects the D-Asp formation has not yet been examined. Here we report the kinetics of Asp racemization in two model peptides, (Asp-Leu)15 and (Leu-Asp-Asp-Leu)8-Asp, which form -sheet structures and -helical structures, respectively. For the -sheet structures, the activation energy of racemization of Asp residues was 27.3 kcal mol-1, the racemization rate constant at 37 °C was 2.14×10-2 per year and the time required to reach a D/L ratio of 0.99 at 37 °C was 122.6 years as estimated from the Arrhenius equation. For the -helical structures, the activation energy of racemization was 18.4 kcal mol-1, the racemization rate constant 20.02×10-2 per year and the time 13.1 year. These results suggest that Asp residues inserted in -helical peptides are more sensitive to racemization than Asp residues inserted in peptides adopting -sheet structures. The results clearly indicate that the racemization rate of Asp residues in peptides depends on the secondary structure of the host peptide.
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Journal articles
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Submitted on : Tuesday, July 3, 2007 - 3:48:29 PM
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Katsunori Kuge, André Brack, Noriko Fujii. Conformation-Dependent Racemization of Aspartyl Residues in Peptides. Chemistry - A European Journal, Wiley-VCH Verlag, 2007, 13 (19), pp.5617-5621. ⟨10.1002/chem.200601677⟩. ⟨hal-00159584⟩

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