A novel assay for RNA targeted drugs

描述（由申请人提供）：NUBAD， LLC是一家致力于鉴定靶向核酸的治疗药物的药物发现公司。该项目旨在合成和表征一类荧光标记的新型氨基糖苷，这些氨基糖苷在RNA结合时表现出显著的荧光变化。氨基糖苷类是一类有效的抗生素，通过结合核糖体RNA上的一个保守位点来阻断细菌蛋白质的合成。该项目的目的是开发一种创新的基于荧光的a位点靶向药物筛选方法，用于快速筛选RNA结合抗菌药物。

DESCRIPTION (provided by applicant): 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. PUBLIC HEALTH RELEVANCE: 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.