title: Observation of O-H...N scalar coupling across a hydrogen bond in nocathiacin I.
abstract: We report here the observation of O-H...N hydrogen-bond (1h)J(N,OH) scalar coupling in a biologically active natural product. The intramolecular hydrogen bond between the threonine hydroxyl (Thr-OH) group and the thiazolyl nitrogen at the second thiazole ring (Thz-2) in nocathiacin I was directly detected by a 1H-15N HMBC NMR experiment. The magnitude of the scalar coupling constant (1h)J(N,OH) was accurately measured to be 1.8 +/- 0.1 Hz by a J-resolved 1H-15N HMBC experiment. By adding the O-H...N distance restraint, the 3D solution structure of nocathiacin I was refined. The structure refinement indicated that the distance between the Thr-3 hydroxyl hydrogen and the Thz-2 nitrogen is <or=2.50 A in all the refined structures, and there are no NOE restraint violations >or= 0.23 A. The presence of an intramolecular hydrogen bond in nocathiacin I is further supported by a number of NMR parameters and additional NMR experiments. This observation provides valuable information for characterizing molecular conformations, and for studying structure-activity relationships.
authors: Bristol-Myers Squibb Pharmaceutical Research Institute, Wallingford, CT 06942, USA. xiaohua.huang@bms.com
authors: Xiaohua Stella
authors: XS
authors: Huang
authors: Xiaohong
authors: X
authors: Liu
authors: Keith L
authors: KL
authors: Constantine
authors: John E
authors: JE
authors: Leet
authors: Vikram
authors: V
authors: Roongta
mesh_terms: D006859:Hydrogen / Q000737:chemistry*; D006860:Hydrogen Bonding; D036341:Intercellular Signaling Peptides and Proteins; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D008968:Molecular Conformation; D015394:Molecular Structure; D009584:Nitrogen / Q000737:chemistry*; D009587:Nitrogen Isotopes; D010100:Oxygen / Q000737:chemistry*; D010455:Peptides / Q000737:chemistry*
chemical_list: D036341:Intercellular Signaling Peptides and Proteins; D009587:Nitrogen Isotopes; D010455:Peptides; C463319:nocathiacin I; D006859:Hydrogen; D009584:Nitrogen; D010100:Oxygen