How change in chirality prevents β-amyloid type interaction in a protonated cyclic dipeptide dimer. Issue 33 (15th August 2022)

• Record Type: Journal Article
• Authors: Le Barbu-Debus, Katia; Pérez-Mellor, Ariel; Lepère, Valéria; Zehnacker, Anne
• Is Part Of: Physical chemistry chemical physics. Volume 24:Issue 33(2022)
• Page Start: 19783
• Page End: 19791
• Publication Date: 2022-08-15
• Subjects: Chemistry, Physical and theoretical -- Periodicals; 541.3
• DOI: 10.1039/d2cp03110h
• Languages: English
• ISSNs: 1463-9076

Abstract

Abstract : The protonated dimer of cyclo (Phe-His) is studied in a ion trap by IR spectroscopy. A β-sheet interaction exists in cyclo (l Phe-l His) and not in cyclo (l Phe-d His). A change in chirality of one of the residues thus prevents amyloid-type clustering. Abstract : The protonated dimers of the diketopiperazine dipeptide cyclo (l Phe-l His) and cyclo (l Phe-d His) 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 (l Phe-d His), that of cyclo (l Phe-l His) 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.