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Updated: Jul 16, 2026

Nanomechanics of Drug-target Interactions and Antibacterial Resistance Detection
Published on: October 25, 2013
D-Ala-D-lac binding is not required for the high activity of vancomycin dimers against vancomycin resistant
Rishi K Jain1, Joaquim Trias, Jonathan A Ellman
1Department of Chemistry, University of California, Berkeley, California 94720, USA.
Abstract:
Covalent dimerization and oligomerization of vancomycin is an important and extensively used strategy to develop analogues active against vancomycin resistant enteroccoci (VRE). Here, we have carried out investigations to probe the role of peptide binding (Lys-d-Ala-d-Lac) in the high anti-VRE activities of covalently linked vancomycin dimers. Covalent dimers of damaged vancomycin (desleucyl) were prepared, and their anti-VRE activities and binding affinities toward various model peptides were measured. Despite the dramatic loss in affinity toward several model peptides in comparison to the corresponding intact vancomycin dimers, these damaged dimers maintained good activity against VRE. These results strongly suggest that the high anti-VRE activities of covalent vancomycin dimers are conferred from mechanisms other than Lys-d-Ala-d-Lac binding.
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