Raman scattering-based multiconformational analysis for probing the structural differences between acetylcholine and acetylthiocholine.
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.
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.
Belén
B
Hernández
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.
Pascal
P
Houzé
Groupe de Biophysique Moléculaire, Sorbonne Paris Cité, Université Paris 13, UFR Santé-Médecine-Biologie Humaine, 74 Rue Marcel Cachin, 93017 Bobigny Cedex, France.
Fernando
F
Pflüger
CNRS UMR 8237, Laboratoire Jean-Perrin, Sorbonne Universités, UPMC Univ. Paris 06, 75005 Paris, France.
Sergei G
SG
Kruglik
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. Electronic address: mahmoud.ghomi@univ-paris13.fr.
Mahmoud
M
Ghomi
D000109:Acetylcholine / Q000737:chemistry*; D000122:Acetylthiocholine / Q000737:chemistry*; D008968:Molecular Conformation; D012996:Solutions / Q000737:chemistry; D013059:Spectrum Analysis, Raman / Q000379:methods*; D014732:Vibration; D014867:Water / Q000737:chemistry
D012996:Solutions; D014867:Water; D000122:Acetylthiocholine; D000109:Acetylcholine
Acetylcholine; Acetylthiocholine; Density functional theory calculations; Implicit and explicit hydration; Multiconformational analysis; Raman scattering