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Title: AVancomycin Derivative with a Pyrophosphate-Binding Group: A Strategy to Combat Vancomycin-Resistant Bacteria
Authors: Yarlagadda, Venkateswarlu
Sarkar, Paramita
Samaddar, Sandip
Haldar, Jayanta
Keywords: Chemistry
bacterial resistance
drug design
multidrug-resistant bacteria
Glycopeptide Antibiotics Back
Cell-Wall Synthesis
D-Lac Binding
Antibacterial Activity
Small Molecules
Issue Date: 2016
Publisher: Wiley-V C H Verlag Gmbh
Citation: Yarlagadda, V.; Sarkar, P.; Samaddar, S.; Haldar, J., AVancomycin Derivative with a Pyrophosphate-Binding Group: A Strategy to Combat Vancomycin-Resistant Bacteria. Angewandte Chemie-International Edition 2016, 55 (27), 7836-7840
Angewandte Chemie-International Edition
Abstract: Vancomycin, the drug of last resort for Gram-positive bacterial infections, has also been rendered ineffective by the emergence of resistance in such bacteria. To combat the threat of vancomycin-resistant bacteria (VRB), we report the development of a dipicolyl-vancomycin conjugate (Dipi-van), which leads to enhanced inhibition of cell-wall biosynthesis in VRB and displays in vitro activity that is more than two orders of magnitude higher than that of vancomycin. Conjugation of the dipicolyl moiety, which is a zinc-binding ligand, endowed the parent drug with the ability to bind to pyrophosphate groups of cell-wall lipids while maintaining the inherent binding affinity for pentapeptide termini of cell-wall precursors. Furthermore, no detectable resistance was observed after several serial passages, and the compound reduced the bacterial burden by a factor of 5 logs at 12 mg kg(-1) in a murine model of VRB kidney infection. The findings presented in this report stress the potential of our strategy to combat VRB infections.
Description: Restricted Access
ISSN: 1433-7851
Appears in Collections:Research Papers (Jayanta Haldar)

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