Probing bacterial uptake of glycosylated ciprofloxacin conjugates

Stephen J Milner; Christopher T Carrick; Kevin G Kerr; Anna M Snelling; Gavin H Thomas; Anne-Kathrin Duhme-Klair; Anne Routledge

doi:10.1002/cbic.201300512

Probing bacterial uptake of glycosylated ciprofloxacin conjugates

Stephen J Milner, Christopher T Carrick, Kevin G Kerr, Anna M Snelling, Gavin H Thomas, Anne-Kathrin Duhme-Klair, Anne Routledge

Research output: Contribution to journal › Article › peer-review

Abstract

Mono- and disaccharide-functionalised conjugates of the fluoroquinolone antibiotic ciprofloxacin have been synthesised and used as chemical probes of the bacterial uptake of glycosylated ciprofloxacin. Their antimicrobial activities against a panel of clinically relevant bacteria were determined: the ability of these conjugates to inhibit their target DNA gyrase and to be transported into the bacteria was assessed by using in vivo and in vitro assays. The data suggest a lack of active uptake through sugar transporters and that although the addition of monosaccharides is compatible with the inhibition of DNA gyrase, the addition of a disaccharide results in a significant decrease in antimicrobial activity.

Original language	English
Pages (from-to)	466-471
Number of pages	6
Journal	Chembiochem
Volume	15
Issue number	3
Early online date	21 Jan 2014
DOIs	https://doi.org/10.1002/cbic.201300512
Publication status	Published - 10 Feb 2014

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10.1002/cbic.201300512

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title = "Probing bacterial uptake of glycosylated ciprofloxacin conjugates",

abstract = "Mono- and disaccharide-functionalised conjugates of the fluoroquinolone antibiotic ciprofloxacin have been synthesised and used as chemical probes of the bacterial uptake of glycosylated ciprofloxacin. Their antimicrobial activities against a panel of clinically relevant bacteria were determined: the ability of these conjugates to inhibit their target DNA gyrase and to be transported into the bacteria was assessed by using in vivo and in vitro assays. The data suggest a lack of active uptake through sugar transporters and that although the addition of monosaccharides is compatible with the inhibition of DNA gyrase, the addition of a disaccharide results in a significant decrease in antimicrobial activity.",

author = "Milner, {Stephen J} and Carrick, {Christopher T} and Kerr, {Kevin G} and Snelling, {Anna M} and Thomas, {Gavin H} and Anne-Kathrin Duhme-Klair and Anne Routledge",

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AU - Milner, Stephen J

AU - Carrick, Christopher T

AU - Kerr, Kevin G

AU - Snelling, Anna M

AU - Thomas, Gavin H

AU - Duhme-Klair, Anne-Kathrin

AU - Routledge, Anne

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AB - Mono- and disaccharide-functionalised conjugates of the fluoroquinolone antibiotic ciprofloxacin have been synthesised and used as chemical probes of the bacterial uptake of glycosylated ciprofloxacin. Their antimicrobial activities against a panel of clinically relevant bacteria were determined: the ability of these conjugates to inhibit their target DNA gyrase and to be transported into the bacteria was assessed by using in vivo and in vitro assays. The data suggest a lack of active uptake through sugar transporters and that although the addition of monosaccharides is compatible with the inhibition of DNA gyrase, the addition of a disaccharide results in a significant decrease in antimicrobial activity.

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