DNA PHOTOLESION STRUCTURE ACTIVITY RELATIONSHIPS

尽管它的许多有毒、诱变和致癌作用 阳光可以归因于DNA光产物，生物体 个别照相产品的活动情况尚不清楚。要确定 精确的结构-活性关系，我们已经确定了 DNA感光产品的结构和开发的积木 DNA光产物在寡核苷酸中的定点掺入 通过自动合成。这些独特的光损伤寡核苷酸 然后用来构建(A)用于高场2D核磁共振的短双链 和模型研究，(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)抗原 产生光产物靶向催化抗体，即， 人工修复酶。目前正在进行的是对 富含T的4、6和8聚体寡核苷酸 串联质谱仪区分能力的评价 异构体，用于分析异构体的混合物，并与高效液相色谱结合 对齐聚物进行测序，并确定其结构 光损伤齐聚物

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