Binding of vancomycin group antibiotics to D-alanine and D-lactate presenting self-assembled monolayers.
Peptides terminating in -Lys-D-Ala-D-Ala, -Lys-D-Ala-L-Ala and -Lys-D-Ala-D-Lactate were covalently coupled via an N-terminal aminohexanoic acid linker to a self-assembled monolayer of HS(CH2)15CO2H on a thin gold film. Binding of the glycopeptide antibiotics vancomycin and chloroeremomycin to these surfaces was then measured using a surface plasmon resonance biosensor. Both antibiotics bound with micromolar affinity to the D-Ala-terminating surface and with millimolar affinity to the D-Lactate-terminating surface. Increasing density of these covalently attached peptides on the surface had no effect on the resultant affinities of either antibiotic for the surface. In contrast, when the lipid-anchored peptide N-alpha-docosanoyl-epsilon-acetyl-Lys-D-Ala-D-Ala was inserted into a supported lipid monolayer, the affinity of the strongly dimerizing antibiotic chloroeremomycin for the surface showed a dependence on ligand density. This was not the case with the weakly dimerizing antibiotic vancomycin. The lipid monolayer surface, which is a more realistic model of the surface of a bacterium, was thus better suited for the study of the cooperative binding interactions that occur between dimeric glycopeptide antibiotics and surface-bound ligands.
Cooper
M A
MA
Department of Chemistry, University Chemical Laboratory, Cambridge, UK.
Fiorini
M T
MT
Abell
C
C
Williams
D H
DH
D000409:Alanine / Q000378:metabolism*; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000378:metabolism*; D001665:Binding Sites; D019281:Dimerization; D005227:Fatty Acids / Q000737:chemistry / Q000378:metabolism; D006860:Hydrogen Bonding; D007700:Kinetics; D019344:Lactic Acid / Q000378:metabolism*; D010455:Peptides / Q000737:chemistry* / Q000378:metabolism*; D010457:Peptidoglycan / Q000737:chemistry / Q000378:metabolism; D010713:Phosphatidylcholines / Q000378:metabolism; D011485:Protein Binding; D020349:Surface Plasmon Resonance; D014640:Vancomycin / Q000031:analogs & derivatives / Q000737:chemistry / Q000378:metabolism*
D000900:Anti-Bacterial Agents; D005227:Fatty Acids; D010455:Peptides; D010457:Peptidoglycan; D010713:Phosphatidylcholines; C112142:chloroeremomycin; D019344:Lactic Acid; D014640:Vancomycin; D000409:Alanine