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Sensors 2017, 17(11), 2598; doi:10.3390/s17112598

Design and Evaluation of Novel Polymyxin Fluorescent Probes

1
Drug Delivery, Disposition and Dynamics, Monash University, Parkville, Victoria 3052, Australia
2
Medicinal Chemistry, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria 3052, Australia
3
Monash Biomedicine Discovery Institute, Department of Microbiology, Monash University, Clayton, Victoria 3800, Australia
*
Authors to whom correspondence should be addressed.
Received: 12 October 2017 / Revised: 6 November 2017 / Accepted: 9 November 2017 / Published: 11 November 2017
(This article belongs to the Special Issue Fluorescent Probes and Sensors)
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Abstract

Polymyxins (polymyxin B and colistin) are cyclic lipopeptide antibiotics that serve as a last-line defence against Gram-negative “superbugs”. In the present study, two novel fluorescent polymyxin probes were designed through regio-selective modifications of the polymyxin B core structure at the N-terminus and the hydrophobic motif at positions 6 and 7. The resulting probes, FADDI-285 and FADDI-286 demonstrated comparable antibacterial activity (MICs 2–8 mg/L) to polymyxin B and colistin (MICs 0.5–8 mg/L) against a panel of gram-negative clinical isolates of Acinetobacter baumannii, Klebsiella pneumoniae and Pseudomonas aeruginosa. These probes should prove to be of considerable utility for imaging cellular uptake and mechanistic investigations of these important last-line antibiotics. View Full-Text
Keywords: polymyxins; fluorescent; dansyl; probe; gram-negative polymyxins; fluorescent; dansyl; probe; gram-negative
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Yun, B.; Roberts, K.D.; Thompson, P.E.; Nation, R.L.; Velkov, T.; Li, J. Design and Evaluation of Novel Polymyxin Fluorescent Probes. Sensors 2017, 17, 2598.

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