title: Conformational studies of resin-bound vancomycin and the complex of vancomycin and Ac2-L-Lys-D-Ala-D-Ala.
abstract: The molecular target of vancomycin, a commonly used glycopeptide antibiotic, is the D-Ala-D-Ala dipeptide subunit on the bacterial cell wall. The molecular basis of interaction between vancomycin and D-Ala-D-Ala in solution is well-known. However, there is no structural data on vancomycin, and its interaction with D-Ala-D-Ala when the drug is tethered to a solid support. In this Article, vancomycin was directly coupled onto TentaGel or PEGA resin through its C terminus. High-resolution magic angle spinning NMR studies indicated that conformation of PEGA bead-bound vancomycin is identical to that of the free drug. Broadening and shifts of the same proton resonances were observed in solution-phase vancomycin or PEGA-bound vancomycin when complexed with Ac(2)-L-Lys-D-Ala-D-Ala. This study demonstrates that bead-bound molecules can behave the same as solution-phase molecules in terms of molecular interaction with its target molecule, thus validating the on-bead screening approach of the "one-bead-one-compound" combinatorial library method.
authors.affiliation: Chinese Academy of Medical Sciences & Peking Union Medical College, Institute of Materia Medica, 1 Xian Nong Tan Street, Beijing 100050, P. R. China.
authors.forename: Nian-Huan
authors.initials: NH
authors.lastname: Yao
authors.forename: Wen-Yi
authors.initials: WY
authors.lastname: He
authors.forename: Kit S
authors.initials: KS
authors.lastname: Lam
authors.forename: Gang
authors.initials: G
authors.lastname: Liu
mesh_terms: D020650:Combinatorial Chemistry Techniques; D009682:Magnetic Resonance Spectroscopy; D008968:Molecular Conformation; D009842:Oligopeptides / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000737:chemistry; D012117:Resins, Synthetic / Q000737:chemistry*; D013696:Temperature; D014640:Vancomycin / Q000737:chemistry*
chemical_list: D009842:Oligopeptides; D012117:Resins, Synthetic; C033530:N(alpha), N-(epsilon)-diacetyl-lysyl-alanyl-alanine; C109511:bis(polyoxyethylene bis(amine)); D011092:Polyethylene Glycols; D014640:Vancomycin