NUBAD, LLC is a drug discovery company devoted to identifying therapeutic agents that target nucleic acids. This project is designed to synthesize and characterize a novel class of fluorescently-labeled aminoglycosides that exhibit a dramatic change in fluorescence upon RNA binding. Aminoglycosides are a potent class of antibiotics that block bacterial protein synthesis by binding to a conserved site on ribosomal RNA. It is the purpose of the project to develop an innovative fluorescence-based screen for A-site targeted drugs for rapid screening of RNA binding antibacterials.
The aminoglycoside class of antibiotics block bacterial protein synthesis by binding a conserved site on ribosomal RNA. These antibiotics are clinically important agents that combat a broad spectrum of bacterial infections but can cause serious side effects such as kidney damage and hearing loss. The emergence of antibiotic resistance and high level of toxicity associated with the current arsenal of drugs demands the development of efficient methods of screening for novel antibiotics with the desirable properties of high potency and low toxicity. NUBAD, LLC, Pendleton, SC in collaboration with PI's lab, Clemson University, SC, has recently identified a fluorescent neomycin conjugate that is being used to probe drug binding to RNA targets. This proposal describes a phase I project that will determine the technical and scientific feasibility of using a fluorescent-neomycin probe in an innovative screen suitable for a high-throughput screen for new aminoglycoside based antibiotics. This phase I application will develop the probe for high throughput applications and then use the targeted screen to check for assay robustness. Selected compounds will then be checked for antibacterial activity and mechanism of action.
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