Issue 39, 2012

How is the anionic tetrahedral intermediate involved in the isomerization of aspartyl peptides to iso-aspartyl ones? A DFT study on the tetra-peptide

Abstract

An isomerization reaction of a tetra-peptide, Ac-Gly-Asp-Gly-Gly-NHMe → Ac-Gly-isoAsp-Gly-Gly-NHMe, was investigated by DFT calculations. Thirteen water molecules were added to the peptide for simulating proton transfers during the isomerization. As a starting analysis, the number (m) of water molecules participating in ready proton transfers was examined by the use of a small model system, H3C–NH–C([double bond, length as m-dash]O)–CH2–CH2–COOH and (H2O)m. The m = 2 stepwise path was found to be of the smallest activation free energy. On the basis of this result, the first isomerization path of the tetra-peptide was obtained with four elementary processes. The m = 2 proton-transfer pattern is involved in them. A different proton transfer gives the second isomerization path with six elementary processes. The second path (with ionization) is more likely than the first one (without ionization). Formation of the five membered rings of the aminosuccinimidyl-residue and anionic tetrahedral intermediates enhances the encapsulation of H3O+ through the wound tetra-peptide ring. The role of the hydrogen bonds on the encapsulation was discussed in terms of the optimized geometries of proton-transfer transition states and intermediates.

Graphical abstract: How is the anionic tetrahedral intermediate involved in the isomerization of aspartyl peptides to iso-aspartyl ones? A DFT study on the tetra-peptide

Supplementary files

Article information

Article type
Paper
Submitted
08 Jun 2012
Accepted
08 Aug 2012
First published
08 Aug 2012

Org. Biomol. Chem., 2012,10, 8007-8015

How is the anionic tetrahedral intermediate involved in the isomerization of aspartyl peptides to iso-aspartyl ones? A DFT study on the tetra-peptide

S. Yamabe, W. Guan and S. Sakaki, Org. Biomol. Chem., 2012, 10, 8007 DOI: 10.1039/C2OB26106E

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