Institut des Sciences Moléculaires d'Orsay (ISMO), CNRS, Université Paris-Saclay, F-91405 Orsay, France.
Phys Chem Chem Phys. 2022 Aug 24;24(33):19783-19791. doi: 10.1039/d2cp03110h.
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.
通过激光光谱学与质谱联用研究了二酮哌嗪二肽环（LPhe-LHis）和环（LPhe-DHis）的质子化二聚体，以阐明立体化学对环状二肽聚集倾向的影响。实验中在氢化物伸缩区域观察到的明显光谱差异很好地解释了 DFT 计算的结果。两种非对映异构体的质子化二聚体都涉及一个强的离子氢键，即一个单体的质子化咪唑环与另一个单体的中性咪唑氮之间的氢键。虽然这种强相互作用伴随着两个部分之间酰胺官能团之间的单个 NH⋯O 氢键，但对于环（LPhe-DHis）的质子化二聚体，环（LPhe-LHis）的质子化二聚体涉及两个 NH⋯O 相互作用，形成反平行 β 片层的模式。因此，残基手性的变化阻止了在淀粉样类型聚集中观察到的β片层模式的形成。这些结果强调了组氨酸残基在肽结构和相互作用中的特殊作用。
