SYNTHETIC STRATEGIES FOR ANTI-VIRAL DRUG DESIGN

这项研究将开发出一种化合物， 流感病毒进入细胞（以及从细胞脱离）。 其目标是： .开发唾液酸类似物的合成路线， 相关化合物，并使用这些化合物来阻断唾液酸 病毒血凝素（HA）和神经氨酸酶（NA）的结合位点。 .为了制备这些化合物的二价、三价和多价形式， 它们与HA和NA之间协同多价相互作用的优势 在病毒的表面。 .通过自由基聚合制备聚合的多价化合物 含有唾液酸类似物的适当官能化的单体 酸，并评估“空间抑制”的结合的重要性， 将病毒转化为细胞。 .开发和实施与这些相关的新型检测方法， 相互作用，包括基于含胚鸡蛋和 亲和毛细管电泳 .开始扩展学习中建立的一般原则 流感病毒与其它病毒和细菌病原体的结合。

This research will develop compounds that interfere with attachment of influenza virus to cells (and detachment from cells). Its objectives are: . To develop synthetic routes to analogs of sialic acids and structurally related compounds, and to use these compounds to block the sialic acid binding sites of viral hemagglutinin (HA) and of neuraminidase (NA). . To prepare bi, tri-, and multivalent versions of these compounds, to take advantage of cooperative polyvalent interaction between them and HA and NA on the surface of the virus. . To prepare polymeric, polyvalent compounds by free-radical polymerization of appropriately functionalized monomers containing analogs of sialic acids, and to evaluate the importance of "steric inhibition" of binding of virus to cell using these polymers. . To develop and implement new types of assays relevant to these interactions, including assays based on embryonated chicken eggs and on affinity capillary electrophoresis. . To begin to extend the general principles established in studying influenza virus to other viruses and to bacterial pathogens.