Issue 33, 2022

How change in chirality prevents β-amyloid type interaction in a protonated cyclic dipeptide dimer

Abstract

The protonated dimers of the diketopiperazine dipeptide cyclo (LPhe-LHis) and cyclo (LPhe-DHis) are studied by laser spectroscopy combined with mass spectrometry to shed light on the influence of stereochemistry on the clustering propensity of cyclic dipeptides. The marked spectroscopic differences experimentally observed in the hydride stretch region are well accounted for by the results of DFT calculations. Both diastereomeric protonated dimers involve a strong ionic hydrogen bond from the protonated imidazole ring of one monomer to the neutral imidazole nitrogen of the other. While this strong interaction is accompanied by a single NH⋯O hydrogen bond between the amide functions of the two moieties for the protonated dimer of cyclo (LPhe-DHis), that of cyclo (LPhe-LHis) involves two NH⋯O interactions, forming the motif of an antiparallel β sheet. Therefore, a change in chirality of the residue prevents the formation of the β sheet pattern observed in the amyloid type aggregation. These results emphasize the peculiar role of the histidine residue in peptide structure and interaction.

Graphical abstract: How change in chirality prevents β-amyloid type interaction in a protonated cyclic dipeptide dimer

Supplementary files

Article information

Article type
Paper
Submitted
08 Jul 2022
Accepted
05 Aug 2022
First published
09 Aug 2022
This article is Open Access
Creative Commons BY-NC license

Phys. Chem. Chem. Phys., 2022,24, 19783-19791

How change in chirality prevents β-amyloid type interaction in a protonated cyclic dipeptide dimer

K. Le Barbu-Debus, A. Pérez-Mellor, V. Lepère and A. Zehnacker, Phys. Chem. Chem. Phys., 2022, 24, 19783 DOI: 10.1039/D2CP03110H

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