RELATIONSHIP BETWEEN DNA STRUCTURE AND ADDUCT FORMATION

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。致癌物和抗肿瘤药物与双链DNA的平衡结合和共价相互作用涉及复杂的空间和电子因素，目前尚不清楚。这项研究将提供新的基本信息：(A)抗肿瘤DNA交联剂序列特异性的起源；(B)如何设计有效的DNA交联剂；(C)DNA与带电物种(包括碱性氨基酸侧链)的相互作用如何引起DNA变形。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The equilibrium binding and covalent interactions of carcinogens and antineoplastic agents with double-stranded DNA involves complex steric and electronic factors that are not well understood. This study will provide new and fundamental information on (a) the origin of the sequence specificity of antineoplastic DNA crosslinking agents; (b) how to design efficient DNA crosslinking agents; and (c) how the interaction of DNA with charged species, including basic amino acid sidechains, can induce DNA deformation.