Solid state synthesis and applications of oligo(phenylene-ethynes)

描述（由申请人提供）： 摘要：低聚的、共轭的水溶性（对亚苯基乙炔）（“OPEs”）在长波长下是强荧光的，并且通过与适当的小分子相互作用是“超猝灭的”。然而，它们和聚合物形式（“PPE”）作为水溶液中的生物分子探针具有显著的缺点。它们是长棒状（大体积）结构，并显示相当大的温度和盐浓度的依赖性，在其荧光性质作为在水溶液中聚集的结果。 我们已经制备了这种类型的最小长度低聚物，“3.5-mer”[基于用苯基封端的三个重复亚苯基-乙炔单元，即“0.5单元”]，其具有显著的荧光产率并且在水中不显示其荧光的温度和盐依赖性。后一种性质使得这种和相关的“OPE3.5”低聚物潜在地可用作研究生物分子相互作用的探针。我们将使用一种高效的固态合成方法来制备有限家族的特异性高荧光寡聚物-寡聚（对苯乙炔）（“OPEs”）。这些化合物在一端具有一个游离的羧基，使它们能够共价连接到生物分子如蛋白质和核酸上。为了评估它们的潜在效用，将一种寡聚体与药物结合蛋白人血清白蛋白（HSA）缀合，并且通过观察作为浓度的函数的荧光变化（即猝灭）来测量构建体与典型药物的相互作用。 该项目的具体目标是：1.固相合成了四种末端羧基取代的“OPE3.5- mers”; 2.表征了合成化合物的荧光性质（激发和发射光谱、量子产率、聚集的可能性）; 3.活化并共价连接选择的寡聚体到人血清白蛋白（HSA），并表征产物的化学计量和荧光性质，和4。研究与典型白蛋白结合药物的相互作用对HSA-寡聚体缀合物的荧光的影响。 已经报道了相关的疏水和亲水（即水溶性）聚合物的合成和性质，但是还没有报道相关的低聚物的系统研究。因此，它们作为生物分子探针的潜力尚未开发。新的低聚物和它们的反应性衍生物将代表分析开发的突破，并将提供给公司和研究机构销售，以发现这些材料的新应用。 公共卫生相关性： 叙述：我们将合成四种特定的共轭低聚化合物，并研究它们的荧光性质。这些寡聚体将被“激活”，其中一个将被连接到一个重要的药物结合蛋白-人血清白蛋白-以测试其作为传感器的前景，以研究其与药物和其他小分子的相互作用。这些新型低聚物及其反应性衍生物将提供给公司和研究机构，以发现这些材料的新应用。

DESCRIPTION (provided by applicant): ABSTRACT: Oligomeric, conjugated water soluble (p-phenylene-ethynes) ("OPEs") are strongly fluorescent at long wavelengths and are "superquenchable" by interaction with appropriate small molecules. They and the polymeric versions ("PPEs"), however, have significant drawbacks as biomolecular probes in aqueous solution. They are long rodlike (bulky) structures and display considerable temperature- and salt concentration-dependence in their fluorescence properties as a result of aggregation in aqueous solutions. We have prepared a minimal length oligomer of this type, a "3.5-mer" [based on three repeating phenylene-ethyne units capped with a phenyl group, i.e. "0.5 unit"], that has significant fluorescence yield and does not show the temperature and salt-dependence of its fluorescence in water. The latter property makes this and related "OPE3.5" oligomers potentially useful as probes for study of biomolecular interactions. We will use an efficient, solid state synthesis approach to prepare a limited family of specific, highly fluorescent oligomers - oligo(p-phenylene-ethyne)s ("OPEs"). The compounds will possess a free carboxyl group at one terminus, enabling them to be covalently attached to biomolecules such as proteins and nucleic acids. In order to assess their potential utility, one oligomer will be conjugated to the drug- binding protein human serum albumin (HSA), and the interaction of the construct with typical drugs will be measured by observing changes in fluorescence, i.e. quenching, as a function of concentration. The specific aims of this project are to: 1. conduct solid state synthesis of four substituted "OPE3.5- mers" containing terminal carboxy groups; 2.characterize the fluorescence properties (excitation and emission spectra, quantum yield, potential for aggregation) of the synthesized compounds; 3. Activate and covalently attach a selected oligomer to human serum albumin (HSA), and characterize the stoichiometries and fluorescence properties of the products, and 4. Study the effect of interaction with typical albumin-binding drugs on the fluorescence of the HSA-oligomer conjugates. The synthesis and properties of related hydrophobic and hydrophilic, i.e. water soluble, polymers have been reported, but no systematic studies of related oligomers have been reported. Thus, their potential as biomolecular probes is unexplored. The novel oligomers and their reactive derivatives will represent breakthroughs in assay development, and will be offered for sale to companies and research institutions for discovery of new applications of these materials. PUBLIC HEALTH RELEVANCE: NARRATIVE: We will synthesize four specific conjugated, oligomeric compounds, and study their fluorescence properties. The oligomers will be "activated" and one will be attached to an important drug-binding protein - human serum albumin - to test its promise as a sensor to study its interaction with drugs and other small molecules. Such novel oligomers and their reactive derivatives will be offered to companies and research institutions for discovery of new applications of these materials.