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（改编自申请）：磷酸肌醇多磷酸盐（PtdInsPns，或简称 PIPns）通过磷酸酶和激酶的相互作用生物合成，是细胞通讯中的关键信号分子。申请人已经合成并向世界各地的研究人员提供了具有生物学意义的“匹配组”的PIPns衍生物，从而实现了其第一层战略。在第一阶段，我们优化了具有四个二酰基部分的 PIPns 的合成和表征：(i) 短链胶束形成类似物，(ii) 中间链两亲性（或水溶性）类似物，(iii) 长链胶束形成类似物，和（iv）连接有报告基团的氨基官能化链。在第二阶段，我们建议制备用于检测生化和细胞研究中 PIPns 变化的试剂，并用于药物和靶点发现工作。首先，申请人将通过合并两个系列的酰基修饰荧光PIPns（BODIPY和NBD系列）来扩展其产品线，以研究脂质依赖性信号传导途径。其次，申请人将使用酰基功能化的PIPn来制备PIPn的抗原形式，并且我们将使用它们来制备PIPn特异性单克隆抗体。第三，申请人将开发用于定量分析和纯化天然存在的合成和化学修饰的PIPns的固定化氨基糖苷柱。拟议的商业应用： 1. 销售用于基础研究的试剂本身。 2.用于基础研究的抗体本身的销售。 3.新拮抗剂和酶抑制剂的药物发现和遗忘发现。