DNA PHOTOLESION STRUCTURE ACTIVITY RELATIONSHIPS

虽然许多毒性，诱变和致癌作用的 阳光可以归因于DNA的光产物，生物 单个光产物的活性是未知的。 确定 精确的结构-活性关系，我们已经确定了 DNA光产物的结构和开发的积木 DNA光产物定点掺入寡核苷酸 自动合成。 这些独特的光损伤寡核苷酸 然后用于构建（a）用于高场2D NMR的短双链体 和建模研究，（B）用于DNA弯曲研究的聚合物，（c）长 用于体外修复和复制研究的DNA片段，（d）病毒 用于体外突变研究的DNA，以及最近的（e）用于 产生光产物靶向的催化抗体，即， 人工修复酶 目前正在进行调查， 4、6和8聚体寡脱氧核苷酸富集T.我们 评价串联质谱法区分 异构体，分析异构体的混合物，并与HPLC结合 介绍，测序寡聚体，并确定结构， 光损伤低聚物

Although many of the toxic, mutagenic and carcinogenic effects of sunlight can be attributed to DNA photoproducts, the biological activities of individual photoproducts are unknown. To determine the precise structure-activity relationships, we have determined the structure of DNA photoproducts and developed building blocks for the site-specific incorporation of DNA photoproducts into oligonucleotides by automated synthesis. These uniquely photodamaged oligonucleotides are then used to construct (a) short duplexes for high field 2D NMR and modeling studies, (b) polymers for DNA bending studies, (c) long DNA fragments for in vitro repair and replication studies, (d) viral DNA for in vitro mutation studies, and most recently (e) antigens for generating photoproduct-targeted catalytic antibodies, i.e., artificial repair enzymes. Currently underway are investigations of 4, 6, and 8 mer oligodeoxynucleotides that are enriched in T. We are evaluating the capability of tandem mass spectrometry to distinguish isomers, to analyze mixtures of isomers, and, in conjunction with HPLC introduction, to sequence oligomers, and to determine the structure of photodamaged oligomers