Development of Polyvalent Inhibitors of HIV Cell Entry

描述(由申请人提供)：这项拟议研究的目标是研究一种策略，通过使用多价配体呈现方法放大已知抑制剂的效力来阻止艾滋病毒进入细胞。我建议创建用已知的HIV融合多肽抑制剂功能化的聚合物支架，利用基于多价结合的增强亲和力，并比较这些系统防止融合的能力与相应浓度的单价活性配体的能力。这项工作的一个成功结果将证明，在病毒-细胞融合的哺乳动物细胞模型中，连接到聚合物上的配体比单体形式的相同配体(在相同的等量浓度下)更能成功地阻止细胞融合。该项目的第一个目标是开发非常有效的艾滋病毒进入的多价抑制剂，使治疗艾滋病毒感染的新疗法成为可能。该项目的第二个目标是开发廉价的多价艾滋病毒进入抑制剂，至少与目前成本高昂的治疗方法一样有效，以使它们能够得到更广泛的使用。

DESCRIPTION (provided by applicant): The goal of this proposed research is to investigate a strategy to block the entry of HIV into cells by amplifying the potency of known inhibitors using a polyvalent ligand presentation approach. I propose to create polymer scaffolds functionalized with known peptide inhibitors of HIV fusion, to exploit an enhanced avidity based on multivalent binding, and to compare the ability of these systems in preventing fusion with that of corresponding concentrations of the active ligand in monovalent form. A successful outcome of this work would be a demonstration that a ligand (or ligands) attached to a polymer is more successful in preventing cell fusion in a mammalian cell model of virus-cell fusion than is the same ligand (at the same equivalent concentration) in monomeric form. The first goal of this project is to develop extremely potent polyvalent inhibitors of HIV entry that may enable novel therapeutic regimens for the treatment of HIV infection. The second goal of this project is to develop cheap polyvalent inhibitors of HIV entry that are at least as potent as current, cost-prohibitive therapies, to enable their wider use.