NOVEL DRUG DESIGN AND HIGH THROUGHPUT SCREENING

考虑到多重耐药菌株的增加，开发新的抗生素是当务之急 在结核病、疟疾、艾滋病等疾病中，以及迄今未知疾病的出现，如 非典。传染性疾病，特别是那些涉及抗药性病原体的疾病，已经恶化。 由于社会经济因素，在少数群体中造成了广泛的健康差距。我们的龙 学期目标是发现和开发新的抗生素来对抗传染病(特别是那些 (由耐药病原体引起)，有助于消除健康差距的努力。作为一名 少数民族院校研究基础设施申请(RIMI)计划支持的子项目，WE 建议通过互补和综合的新方法来推进抗生素药物的发现 寄主防御、微生物基因组和基本分子识别观点。在……里面 特别是，我们将评估天然宿主防御类脂作为抗菌疗法的潜力， 我们最近的实验数据支持脂质在体内的新的防御作用的基础。在另一个人身上 在这方面，我们将利用增加的研究能力来确定更多的新化学结构 通过高通量筛选不同化合物文库的抗微生物活性。期待一场 稳定提供有效的抗菌化合物，我们将尝试开发一种新型的更高效的抗菌药物 确定这些有效抑制物(包括基于脂质的抑制物)的细胞靶标的方法 调节必要的靶蛋白的表达。此外，我们还将对分子进行探测和评估 阳离子-pi相互作用作为一种潜在的配体-蛋白质识别和结合的新机制，结果 这将为那些新发现的和合理的药物设计提供新的见解和策略 优先选择抗菌药物靶标-抑制物对。有来自内部和外部导师的指导和访问 通过RIMI基金实现高通量筛选和化学/分子分析仪器 机制，调查人员将能够建立一个新颖和集成的药物发现平台，将 有助于抗击抗药性病原体，并努力消除 少数族裔人口。

Development of novel antibiotics is of utmost urgency, considering the increase in multi-drug resistant strains in diseases like tuberculosis, malaria, AIDS, and the emergence of hitherto unknown diseases such as SARS. Infectious diseases, especially those that involve drug resistant pathogens, have been exacerbated by socioeconomic factors, resulting in widespread health disparities among minority populations. Our long term objective is to discover and develop novel antibiotics to combat infectious diseases (in particular those caused by drug resistant pathogens), contributing to the effort of elimination of health disparities. As a subproject of an application for Research Infrastructure in Minority Institutions (RIMI) Program support, we propose to advance antibiotic drug discovery through complementary and integrated novel approaches from the host defense, the microbial genomic, and the fundamental molecular recognition perspectives. In particular, we will assess the potential of natural host defense lipids as antimicrobial therapeutics, building on the foundation of our recent experimental data in support of lipids' novel in vivo defensive roles. On another front, we will leverage the increased research capacity to identify additional novel chemical structures with antimicrobial activities through high throughput screening of diverse compound libraries. Anticipating a steady provision of potent antibacterial compounds, we will attempt to develop a novel and more efficient method of identifying the cellular targets for these potent inhibitors (including lipid-based inhibitors) through modulated expression of essential target proteins. Furthermore, we will probe and evaluate the molecular cation-pi interaction as a potential novel mechanism of ligand-protein recognition and binding, the result of which would provide new insight and strategies for rational drug design for those newly discovered and prioritized antimicrobial target-inhibitor pairs. With guidance from internal and external mentors and access to high throughput screening and chemical/molecular analysis instrumentation through RIMI funding mechanism, the investigators will be able establish a novel and integrated drug discovery platform that will contribute to the fight against drug resistant pathogens and the effort to eliminate health disparities among minority populations.