PERTUBATION OF RIBOSOMAL FRAMESHIFTING

核糖体移码的扰动

• 批准号: 6210309
• 负责人: SERGUEI Y GOLOVINE
• 金额: $ 10万
• 依托单位: PINNACLE PHARMACEUTICALS
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-08-01 至 2001-10-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6210309
• 关键词: chemical synthesis; frameshift mutation; human immunodeficiency virus 1; inhibitor /antagonist; intermolecular interaction; nucleic acid sequence; plant extracts; reporter genes; ribosomal RNA; virus RNA; virus protein; virus replication

The overall goal of this SBIR is to identify small molecules that can perturb ribosomal frameshifting at the gag-pol junction in HIV- 1 - These may have practical applications, e.g. in the treatment of individuals infected with HIV- 1. The approach involves the screening of natural product extract libraries and synthetic compounds for agents that can perturb frameshifting in a model system predictive of frameshifting behavior during HIV-1 replication. Those extracts found to affect frameshifting will be subjected to bioassay-guided fractionation to permit isolation of the active principle(s). These principles will be obtained in quantities sufficient for evaluation as anti HIV-1 agents and characterized to evaluate their biological properties. If we are able to identify agents that perturb ribosomal frameshifting at the gag-poljunction and thereby affect HIV-1 replication, the effort will be expanded to conduct a focused search for agents potentially efficacious in the treatment of HIV- 1 infection. PROPOSED COMMERCIAL APPLICATIONS: This technology is intended to lead to agents that can be utilized therapeutically for the treatment of HIV-1 -infected individuals.

该 SBIR 的总体目标是识别可以扰乱 HIV-1 中 gag-pol 连接处核糖体移码的小分子 - 这些可能具有实际应用，例如该方法涉及筛选天然产物提取物库和合成化合物，以寻找能够干扰预测 HIV-1 复制期间移码行为的模型系统中移码的药物。那些被发现影响移码的提取物将进行生物测定引导的分级分离，以分离活性成分。这些原理的获得量足以用于评估抗 HIV-1 药物，并进行表征以评估其生物特性。如果我们能够识别干扰核糖体移码的药物，从而影响HIV-1复制，我们将加大努力，重点寻找可能有效治疗HIV-1感染的药物。拟议的商业应用：该技术旨在开发可用于治疗 HIV-1 感染个体的药物。