Cooperativity between non-polar and ionic forces in the binding of bacterial cell wall analogues by vancomycin in aqueous solution.
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.
Cristofaro
M F
MF
Cambridge Centre for Molecular Recognition, University Chemical Laboratory, England.
Beauregard
D A
DA
Yan
H
H
Osborn
N J
NJ
Williams
D H
DH
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
D012996:Solutions; D014640:Vancomycin