Conformational studies of resin-bound vancomycin and the complex of vancomycin and Ac2-L-Lys-D-Ala-D-Ala

J Comb Chem. 2005 Jan-Feb;7(1):123-9. doi: 10.1021/cc0498783.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Combinatorial Chemistry Techniques
  • Magnetic Resonance Spectroscopy
  • Molecular Conformation
  • Oligopeptides / chemistry*
  • Polyethylene Glycols / chemistry
  • Resins, Synthetic / chemistry*
  • Temperature
  • Vancomycin / chemistry*

Substances

  • Oligopeptides
  • Resins, Synthetic
  • N(alpha), N-(epsilon)-diacetyl-lysyl-alanyl-alanine
  • bis(polyoxyethylene bis(amine))
  • Polyethylene Glycols
  • Vancomycin