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.

在有机动力学项目的支持下，霍普金斯博士 将研究两个DNA链间的化学结构 交联，即，由DNA反应产生的那些（i） 与氮芥和（ii）与还原性的类似物 活化丝裂霉素C研究了该机制， 所述丝裂霉素类似物优先交联5 ′-CG DNA中的序列将沿着进行的研究， 其他几种链间DNA的序列偏好 交联剂 %%% DNA链间共价交联反应涉及 将DNA上的亲核中心加到亲电中心上， 交联剂的中心。这些基本上是 简单的化学反应发生在一个结构和 动态复杂大分子。霍普金斯博士的研究 旨在提供有关共价键的信息， 交联DNA在核苷酸水平上的结构， 某些情况将提供有关原子的信息 连通性霍普金斯医生从 这些研究可能会导致简化， 改进新的DNA交联剂的设计。