Sequence Preferences of DNA Interstrand Crosslinkers

在有机动力学项目的支持下，霍普金斯博士将研究两种DNA链交联的化学结构，即，DNA (i)与氮芥和（ii）与还原激活丝裂霉素c的类似物反应产生的反应。丝裂霉素类似物优先交联DNA中5'-CG序列的机制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上的亲核中心加成到交联剂的亲电中心上。这些基本上是发生在结构和动态复杂的大分子上的简单化学反应。霍普金斯博士的研究旨在提供核苷酸水平上交联dna共价结构的信息，并在某些情况下提供有关原子连通性的信息。霍普金斯博士从这些研究中获得的信息可能会导致新的DNA交联剂设计的简化和改进。

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.