SOLUBLE AND ANTIGENIC PHOSPHOINOSITIDE PHOSPHATES

描述（改编自本申请）：磷酸肌醇多磷酸（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全世界的研究人员提供了具有生物学意义的PIPns衍生物的“匹配组”，从而实现了其第一层策略。在阶段I期间，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（或水溶性）类似物，（iii）长链胶束形成类似物，和（iv）附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，申请人将扩大其产品线，纳入两个系列的酰基修饰的荧光PIPns，BODIPY和NBD系列，以研究脂质依赖性信号通路。其次，申请人将使用酰基官能化的PIPn来制备PIPn的抗原形式，并且我们将使用这些来制备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PIPn的固定化β-氨基糖苷类柱。建议的商业应用：1.销售用于基础研究的试剂。2.销售抗体本身用于基础研究。3.新拮抗剂和酶抑制剂的药物发现和遗忘发现。

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.