Issue 7, 2014

Conformational preferences of the 2-methylproline residue and its role in stabilizing β-turn and polyproline II structures of peptides

Abstract

Conformational preferences of the 2-methylproline (2-MePro) residue and its role in stabilizing β-turn and polyproline II (PII) structures of peptides have been studied using density functional methods in the gas phase and in water. The population of the C7 H-bonded structures of Ac-2-MePro-NHMe is calculated to be dominant in the gas phase, whereas they become significantly depopulated and the populations of polyproline and α-helical structures increase in water. Due to the increased stability of the up-puckered PII structure, the populations of its PII and PI structures are more increased by 10.9% and decreased by 12.2% than Ac-Pro-NHMe in water, respectively. There is a large decrease in the cis population by 20.6% for the prolyl peptide bond by replacing Pro with 2-MePro in water, which is consistent with 13C NMR experiments. For Ac-Ala-2-MePro-NHMe, the conformer with a βI-turn is found to be the most preferred conformer with the population of 25.2% in water, whereas the open conformers are dominantly populated for Ac-Ala-Pro-NHMe. This is consistent with experimental results that the Ala-Pro sequence of the antigen mimotope associated with autoimmune recurrent thrombosis has been known to adopt a stable βI-turn structure with the replacement of Pro by 2-MePro in water. With the replacement of a single Pro by 2-MePro in the middle of the sequences of the polyproline model peptide Ac-(Pro)5-NMe2 and the single-strand model peptide of collagen Ac-(Hyp-Gly-Pro)2-NMe2, the relative stabilities of the PII structures are enhanced by 8.11 and 3.91 kcal mol−1, respectively, although there are only small changes in backbone torsion angles of both PII and PI structures. It can be deduced that the single strands of (Hyp-Gly-2-MePro)n with the stable PII structure might provide more stability to their triple helix.

Graphical abstract: Conformational preferences of the 2-methylproline residue and its role in stabilizing β-turn and polyproline II structures of peptides

Supplementary files

Article information

Article type
Paper
Submitted
16 Jan 2014
Accepted
27 Mar 2014
First published
27 Mar 2014

New J. Chem., 2014,38, 2831-2840

Conformational preferences of the 2-methylproline residue and its role in stabilizing β-turn and polyproline II structures of peptides

Y. K. Kang and H. S. Park, New J. Chem., 2014, 38, 2831 DOI: 10.1039/C4NJ00072B

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