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Updated: Jul 2, 2026

Nanomechanics of Drug-target Interactions and Antibacterial Resistance Detection
Published on: October 25, 2013
Hydrophobic side-chain length determines activity and conformational heterogeneity of a vancomycin derivative bound
Sung Joon Kim1, Jacob Schaefer
1Department of Chemistry, Washington University, St. Louis, Missouri 63130, USA.
Abstract:
Disaccharide-modified glycopeptides with hydrophobic side chains are active against vancomycin-resistant enterococci and vancomycin-resistant Staphylococcus aureus. The activity depends on the length of the side chain. The benzyl side chain of N-(4-fluorobenzyl)vancomycin (FBV) has the minimal length sufficient for enhancement in activity against vancomycin-resistant pathogens. The conformation of FBV bound to the peptidoglycan in whole cells of S. aureus has been determined using rotational-echo double resonance NMR by measuring internuclear distances from the (19)F of FBV to (13)C and (15)N labels incorporated into the cell-wall peptidoglycan. The hydrophobic side chain and aglycon of FBV form a cleft around the pentaglycyl bridge. FBV binds heterogeneously to the peptidoglycan as a monomer with the (19)F positioned near the middle of the pentaglycyl bridge, approximately 7 A from the bridge link. This differs from the situation for N-(4-(4-fluorophenyl)benzyl)vancomycin complexed to the peptidoglycan where the (19)F is located at the end of pentaglycyl bridge, 7 A from the cross-link.
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