RELATIONSHIP BETWEEN DNA STRUCTURE AND ADDUCT FORMATION

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。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，这些因素尚未得到很好的理解。本研究将为以下方面提供新的基础信息：(a)抗肿瘤DNA交联剂序列特异性的起源；(b)如何设计高效的DNA交联剂；(c) DNA与带电物质（包括碱性氨基酸侧链）的相互作用如何诱导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.