ASERS -Label-Free Assay for AIDS Drug Development

ASERS - 艾滋病药物开发的无标记检测

• 批准号: 6910839
• 负责人: ANN E GROW
• 金额: $ 29.99万
• 依托单位: BIOPRAXIS, INC.
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-07-01 至 2007-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6910839
• 关键词: AIDS; RNA directed DNA polymerase; Raman spectrometry; antiAIDS agent; antiviral agents; computer program /software; conformation; drug design /synthesis /production; drug discovery /isolation; drug screening /evaluation; fluid flow; high throughput technology; human immunodeficiency virus 1; ligands; microfluidics; small molecule

DESCRIPTION (provided by applicant): Biopraxis proposes to develop its mu SERS platform technology as a high-throughput mix-and-measure screening (HTS) assay for antiviral drug lead identification and optimization. Unlike current HTS assays, mu SERS does not rely on labels. Instead, surface-enhanced Raman fingerprints are collected directly from the biomolecule. These fingerprints contain a rich body of information on the chemistries of the biomolecule and any ligands bound to it. Therefore, unlike other technologies which simply determine whether binding takes place, mu SERS can also tell which ligands were bound, and even produce information on how they were bound (i.e., on the binding chemistries involved). HIV-1 reverse transcdptase (RT) will be used as a model system on Phase I to demonstrate the unique capabilities of the technology. On Phase II, mu SERS will be developed into a flexible tool that can be used to screen small molecule libraries against diverse HIV targets (e.g., integrase, trans-activation-responsive RNA, or envelope glycoproteins). The tool will comprise a mu SERS chip reader; a miniature 'nanowell plate' chip and associated microfluidics for handling tiny samples; and software for analysis of small ligands binding any type of biomolecule. The analyses will be exceptionally sensitive, consuming trace amounts of biomolecules and chemical libraries; very rapid, requiring only a single incubation to allow binding to take place, plus a few seconds to collect and process the spectra; and flexible, able to accommodate studies on, e.g., binding interactions with biomolecule complexes, competitive, synergistic, or antagonistic binding, and/or the impact of pH or metal ions on ligand binding interactions.

描述（由申请人提供）：Biopraxis 提议开发其 mu SERS 平台技术，作为一种高通量混合测量筛选（HTS）测定法，用于抗病毒药物先导物识别和优化。与当前的 HTS 检测不同，μ SERS 不依赖于标记。相反，表面增强拉曼指纹是直接从生物分子中收集的。这些指纹包含有关生物分子和与其结合的任何配体的化学成分的丰富信息。因此，与简单确定是否发生结合的其他技术不同，μ SERS 还可以判断哪些配体被结合，甚至产生有关它们如何结合的信息（即有关所涉及的结合化学物质）。 HIV-1逆转录酶（RT）将被用作第一阶段的模型系统，以展示该技术的独特功能。在第二阶段，mu SERS 将发展成为一种灵活的工具，可用于筛选针对不同 HIV 靶标（例如整合酶、反式激活响应 RNA 或包膜糖蛋白）的小分子文库。该工具将包括一个 mu SERS 芯片读取器；用于处理微小样品的微型“纳米孔板”芯片和相关的微流体；以及用于分析结合任何类型生物分子的小配体的软件。分析将异常灵敏，消耗微量的生物分子和化学库；非常快，只需要一次孵育即可发生结合，再加上几秒钟的时间来收集和处理光谱；且灵活，能够适应例如与生物分子复合物的结合相互作用、竞争性、协同性或拮抗性结合、和/或pH或金属离子对配体结合相互作用的影响的研究。