Development of Polyvalent Inhibitors of HIV Cell Entry

HIV细胞进入多价抑制剂的开发

• 批准号: 7064621
• 负责人: DEMETRI T MOUSTAKAS
• 金额: $ 4.6万
• 依托单位: HARVARD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-01-04 至 2008-01-03
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7064621
• 关键词: HIV envelope protein gp120; HIV envelope protein gp41; antiAIDS agent; chemical structure; drug design /synthesis /production; human immunodeficiency virus; ligands; peptide structure; polymers; postdoctoral investigator; virus infection mechanism

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.

描述（由申请人提供）：这项拟议研究的目标是通过使用多价配体呈递方法放大已知抑制剂的效力来研究阻断HIV进入细胞的策略。我建议用已知的HIV融合肽抑制剂制造聚合物支架，利用基于多价结合的增强亲和性，并比较这些系统在防止融合方面的能力与相应浓度的单价形式的活性配体的能力。这项工作的一个成功结果将是证明，在哺乳动物病毒-细胞融合的细胞模型中，与聚合物结合的配体（或配体）比以单体形式结合的相同配体（同等浓度）更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HIV进入多价抑制剂，这可能会为治疗HIV感染提供新的治疗方案。该项目的第二个目标是开发廉价的多价艾滋病病毒进入抑制剂，至少与目前昂贵的治疗方法一样有效，从而使其得到更广泛的应用。