title: Cooperativity between non-polar and ionic forces in the binding of bacterial cell wall analogues by vancomycin in aqueous solution.
abstract: 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.
authors.affiliation: Cambridge Centre for Molecular Recognition, University Chemical Laboratory, England.
authors.forename: M F
authors.initials: MF
authors.lastname: Cristofaro
authors.forename: D A
authors.initials: DA
authors.lastname: Beauregard
authors.forename: H
authors.initials: H
authors.lastname: Yan
authors.forename: N J
authors.initials: NJ
authors.lastname: Osborn
authors.forename: D H
authors.initials: DH
authors.lastname: Williams
mesh_terms: D000595:Amino Acid Sequence; D001419:Bacteria / Q000187:drug effects* / Q000378:metabolism; D001665:Binding Sites; D002473:Cell Wall / Q000187:drug effects* / Q000378:metabolism; D008969:Molecular Sequence Data; D015394:Molecular Structure; D012996:Solutions; D013329:Structure-Activity Relationship; D014640:Vancomycin / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology
chemical_list: D012996:Solutions; D014640:Vancomycin