Sequence Preferences of DNA Interstrand Crosslinkers

DNA 链间交联剂的序列偏好

• 批准号: 9019129
• 负责人: Paul Hopkins
• 金额: $ 10.43万
• 依托单位: University of Washington
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 1991
• 资助国家: 美国
• 起止时间: 1991-04-15 至 1994-09-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=9019129&HistoricalAwards=false
• 关键词: Sequence; Preferences; DNA; Interstrand; Crosslinkers

With support from the Organic Dynamics Program, Dr. Hopkins will study the chemical structures of two DNA interstrand crosslinks, i.e., those that result from reaction of DNA (i) with a nitrogen mustard and (ii) with an analog of reductively activated mitomycin C. An investigation of the mechanism by which mitomycin analogs preferentially crosslink 5'-CG sequences in DNA will be performed along with studies of the sequence preferences of several other interstrand DNA crosslinking agents. %%% DNA interstrand covalent crosslinking reactions involve addition of a nucleophilic center on DNA to an electrophilic center of the crosslinking agent. These are fundamentally simple chemical reactions that take place on a structurally and dynamically complex macromolecule. Dr. Hopkins' study is designed to provide information regarding the covalent structures of crosslinked DNAs at the nucleotide level and in some cases will provide information regarding atomic connectivities. Information that Dr. Hopkins obtained from these studies is likely to lead to simplification and improvement in the design of new DNA crosslinking agents.

在有机动力学计划的支持下，霍普金斯博士将研究两个 DNA 链间交联的化学结构，即由 DNA (i) 与氮芥和 (ii) 与还原激活的丝裂霉素 C 类似物反应产生的交联对丝裂霉素类似物优先交联 DNA 中 5'-CG 序列的机制的研究将与其他几种链间 DNA 交联剂的序列偏好研究一起进行。 %%% DNA 链间共价交联反应涉及将 DNA 上的亲核中心添加到交联剂的亲电中心。这些基本上是在结构和动态复杂的大分子上发生的简单化学反应。霍普金斯博士的研究旨在提供有关核苷酸水平上交联 DNA 共价结构的信息，并在某些情况下提供有关原子连接性的信息。霍普金斯博士从这些研究中获得的信息可能会简化和改进新型 DNA 交联剂的设计。