Development of Polyvalent Inhibitors of HIV Cell Entry

描述（由申请人提供）：本拟议研究的目标是研究一种通过使用多价配体呈递方法放大已知抑制剂的效力来阻断HIV进入细胞的策略。我建议创建聚合物支架功能化与已知的肽抑制剂的HIV融合，利用增强的亲合力的基础上多价结合，并比较这些系统的能力，在防止融合与相应浓度的活性配体的单价形式。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，与单体形式的相同配体（相同当量浓度）相比，与聚合物连接的配体（或多个配体）在防止细胞融合方面更成功。该项目的第一个目标是开发极其有效的HIV进入多价抑制剂，这可能使治疗HIV感染的新治疗方案成为可能。该项目的第二个目标是开发廉价的多价HIV进入抑制剂，至少与目前成本高昂的疗法一样有效，以使其更广泛地使用。

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.