THE ATTACHMENT OF INTERCALATORS TO OLIGODEOXYNUCLEOTIDES

嵌入剂与寡脱氧核苷酸的连接

• 批准号: 3818747
• 负责人: MARK CUSHMAN
• 金额: --
• 依托单位: PURDUE UNIVERSITY
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3818747
• 关键词: AIDS; antiAIDS agent; antiviral agents; chemical binding; chemical structure function; deoxyribopolynucleotide; drug design /synthesis /production; human immunodeficiency virus 1; microorganism disease chemotherapy; phenanthridines; phosphates

A series of novel HTLV-III/LAV (HIV) agents will be synthesized in which intercalating agents are connected covalently to oligodeoxynucleotides through the 5'-phosphate, the 3'-phosphate, and both the 5'- and 3'-phosphates. The intercalating agents have been selected from the protoberberine and benzophenanthridine groups of alkaloids, and they have reverse transcriptase inhibitory properties in their own right. The oligodeoxynucleotides are targeted to critical nucleic acid sequences in the virus. Variation of the point of attachment of the oligodeoxynucleotides to the intercalating agents will result in a variety of potential antiviral agents. In addition, the structures of the intercalating agents and the oligodeoxynucleotides will be varied. The individual agents will posses distinct mRNA binding properties and antiviral activities. An attempt will be made to elucidate the relationship between the structures of the individual agents, their mRNA- binding properties, and their antiviral activities. The emerging biological and physical chemical data will be utilized in the design of more potent and selective antiviral agents.

一系列新颖的HTLV-III/LAV（HIV）代理将合成 哪些互插剂共价连接到 通过5'-磷酸盐，3'-磷酸盐，寡脱氧核苷酸， 以及5'-和3'-磷酸盐。 插剂具有 是从Protoberberine和苯甲烷类中选择的 一组生物碱，它们具有逆转录酶抑制 属性本身。 寡脱氧核苷酸是 针对病毒中的临界核酸序列。 变化 寡脱氧核苷酸的附着点 插入剂将导致各种潜在的抗病毒药物 代理商。 另外，插入剂的结构和 寡脱氧核苷酸将变化。 个别代理 将具有独特的mRNA结合特性和抗病毒 活动。 将尝试阐明这种关系 在单个代理的结构之间，它们的mRNA- 结合特性及其抗病毒活性。 新兴 生物学和物理化学数据将用于设计 更有效和选择性的抗病毒剂。