Hernández Belén, Houzé Pascal, Pflüger Fernando, Kruglik Sergei G, Ghomi Mahmoud
CNRS UMR 7369, Laboratoire Matrice Extracellulaire et Dynamique Cellulaire, Université de Reims Champagne Ardenne, UFR Sciences Exactes et Naturelles, Moulin de la Housse, 51687 Reims Cedex 2, France; Groupe de Biophysique Moléculaire, Sorbonne Paris Cité, Université Paris 13, UFR Santé-Médecine-Biologie Humaine, 74 Rue Marcel Cachin, 93017 Bobigny Cedex, France.
Laboratoire de Biochimie, Hôpital Saint Louis, 1 Avenue Claude Vellefaux, 75010 Paris, France; UTCBS, CNRS UMR8258 - U1022, Université Paris Descartes, Sorbonne Paris Cité, Faculté de Pharmacie, 75006 Paris, France.
J Pharm Biomed Anal. 2017 May 10;138:54-62. doi: 10.1016/j.jpba.2017.01.049. Epub 2017 Jan 27.
Acetylcholine is the first discovered neurotransmitter that has received a great attention regarding its capability of binding to several cellular targets. The chemical composition of acetylcholine, including a positively charged trimethylammonium and a carbonyl group, as well as its conformational flexibility was pointed out as the key factors in the stabilization of its interactions. Here, the possibilities offered by a Raman scattering-based multiconformatioal analysis to access the most stable conformers of acetylcholine, is discussed. To control the validity of this protocol, acetylcholine and one of its closely structured analogues, acetylthiocholine, were simultaneously analyzed. Solution Raman spectra revealed distinct and well resolved strong markers for each molecule. Density functional theory calculations were consistent with the fact that the energy order of the low energy conformers is considerably affected by the acyloxy oxygen→sulfur atom substitution. Raman spectra were calculated on the basis of the thermal average of the spectra arising from the low energy conformers. It has been evidenced that the carbonyl and trimethylammonium groups are the most favorable hydration sites in aqueous environment. Taking into account the large gap between the carbonyl bond-stretch and aliphatic bending bands, Raman spectra also allowed separation of the HOH bending vibrations arising from the bound and bulk water molecules.
乙酰胆碱是最早被发现的神经递质，因其能够与多种细胞靶点结合而备受关注。乙酰胆碱的化学成分，包括带正电荷的三甲铵和羰基，以及其构象灵活性，被指出是稳定其相互作用的关键因素。在此，讨论了基于拉曼散射的多构象分析提供的获取乙酰胆碱最稳定构象的可能性。为了控制该方案的有效性，同时分析了乙酰胆碱及其结构紧密的类似物之一硫代乙酰胆碱。溶液拉曼光谱揭示了每个分子独特且分辨良好的强标记。密度泛函理论计算与低能构象体的能量顺序受酰氧基氧→硫原子取代显著影响这一事实一致。基于低能构象体产生的光谱的热平均值计算了拉曼光谱。已证明羰基和三甲铵基团是水环境中最有利的水合位点。考虑到羰基键伸缩和脂肪族弯曲带之间的大差距，拉曼光谱还允许分离结合水分子和本体水分子产生的 HOH 弯曲振动。
