SOLUBLE AND ANTIGENIC PHOSPHOINOSITIDE PHOSPHATES

可溶性和抗原性磷酸肌醇磷酸盐

• 批准号: 6014904
• 负责人: GLENN DOWNES PRESTWICH
• 金额: $ 27.4万
• 依托单位: ECHELON BIOSCIENCES, INC.
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-05-01 至 2001-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6014904
• 关键词: antigens; biological signal transduction; chemical synthesis; fluorescent dye /probe; monoclonal antibody; phosphatidate phosphatase; phosphatidylinositols; technology /technique development

DESCRIPTION (Adapted from the application): Phosphoinositide polyphosphates (PtdInsPns, or simply PIPns) biosynthesized by the interplay of phosphatases and kinases, are key signaling molecules in cellular communication. The applicant has synthesized and provided "matched sets" of PIPns derivatives of biological interest to researchers worldwide thereby achieving its first tier strategy. During Phase I, we optimized synthesis and characterization of PIPns with four diacyl moieties: (i) short-chain micelle-forming analogs, (ii) intermediate chain amphipathic (or water-soluble) analogs, (iii) long-chain micelle-forming analogs, and (iv) amino-functionalized chains with reporter groups attached. In Phase II, we propose to prepare reagents for the detection of changes in PIPns in biochemical and cellular studies and for use in drug and target discovery efforts. First, the applicant will expand its product line with the incorporation of two series of acyl-modified fluorescent PIPns, the BODIPY and NBD series, to study lipid-dependent signaling pathways. Second, the applicant will employ acyl-functionalized PIPns to prepare antigenic forms of the PIPns and we will use these to prepare PIPn-specific monoclonal antibodies. Third, the applicant will develop immobilized- aminoglycoside columns for the quantitative analysis and purification of naturally occurring synthetic, and chemically modified PIPns. PROPOSED COMMERCIAL APPLICATION: 1. Sale of reagents themselves for basic research. 2. Sales of antibodies themselves for basic research. 3. Drug discovery and forget discovery for new antagonist and enzyme inhibitors.

描述（根据应用程序改编）：通过磷酸酶和激酶的相互作用，磷酸肌醇多磷酸盐（PTDINSPN或简单的PIPNS）生物合成是细胞通信中的关键信号分子。申请人已为全球研究人员合成并提供了生物学兴趣的PIPN衍生物的“匹配集”，从而实现了其第一个层次策略。在第一阶段，我们通过四个二酰基部分优化了PIPN的合成和表征：（i）短链胶束形成类似物，（ii）中间链的两亲两亲性（或水溶）类似物，（iii）长链胶束形成类似物，（iiv）与（IV）氨基官方脉络膜相互连接。在第二阶段，我们建议为检测生化和细胞研究中的PIPN变化以及用于药物和目标发现工作的使用准备试剂。首先，申请人将通过将两个系列酰基修饰的荧光PIPNS（Bodipy和NBD系列）结合起来扩展其产品线，以研究依赖脂质的信号通路。其次，申请人将采用酰基官能化的PIPN来制备PIPN的抗原性形式，我们将使用它们来制备PIPN特异性单克隆抗体。第三，申请人将开发固定的 - 氨基糖苷柱，以进行定量分析和纯化自然发生的合成和化学修饰的PIPN。拟议的商业应用程序：1。销售试剂本身进行基础研究。 2。抗体的销售本身用于基础研究。 3.药物发现并忘记了新的拮抗剂和酶抑制剂的发现。