Cooperativity between non-polar and ionic forces in the binding of bacterial cell wall analogues by vancomycin in aqueous solution

J Antibiot (Tokyo). 1995 Aug;48(8):805-10. doi: 10.7164/antibiotics.48.805.


The clinically important glycopeptide antibiotic vancomycin binds to bacterial cell wall peptides of Gram-positive bacteria which terminate in -Lys-D-Ala-D-Ala, thereby inhibiting cell wall synthesis resulting in cell death. We have removed the N-terminal leucine residue of vancomycin by an Edman degradation and acylated the exposed amino group of residue 2 with N-Me-Gly, N-Me-D-Ala, acetyl, butyl, and isohexyl groups to generate novel vancomycin analogues. The binding of vancomycin and these vancomycin analogues to the bacterial cell wall analogue di-N-Ac-L-Lys-D-Ala-D-Ala (DALAA) was studied by NMR techniques and UV spectroscopy. The effects that these structural modifications of the carboxylate binding pocket of vancomycin have on the antibiotic-DALAA recognition process show that a cooperative effect between non-polar and ionic forces appears to be partly responsible for the highly efficient sequestering of the DALAA C-terminal carboxylate from aqueous solution.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Bacteria / drug effects*
  • Bacteria / metabolism
  • Binding Sites
  • Cell Wall / drug effects*
  • Cell Wall / metabolism
  • Molecular Sequence Data
  • Molecular Structure
  • Solutions
  • Structure-Activity Relationship
  • Vancomycin / analogs & derivatives*
  • Vancomycin / metabolism
  • Vancomycin / pharmacology


  • Solutions
  • Vancomycin