CAREER: Redox-Mediated Cleavage of Peptides and Nucleic Acids

这项无机化学、生物无机化学和金属有机化学计划的职业奖支持马里兰大学巴尔的摩县分校化学和生物化学系的丽莎·凯利教授对一系列亚胺发色团的设计、合成和研究的研究，以光化学方式切割DNA。将以胸腺嘧啶核苷为靶点，并测量鸟嘌呤的裂解。光敏剂将在氧气存在下循环使用，双链核酸裂解将成为可能。大环将共价连接到发色团上，并与各种金属离子配位。这些金属离子将包括锌(II)(嘧啶专有的)、Cd(II)和Pb(II)(重原子)，以及Co(III)和Cu(II)(电子受体)。通过使用这些金属络合物，可以确定光活化后的定点定位、提高激发态三重态产额和电子-空穴分离的效果。这些研究将提供关于核酸聚合物氧化损伤机制的信息，特别是关于氧化还原反应的起始位置和最终切割位置之间的关系的信息。本研究的目标是开发优化的光活性化合物，可以用来以一种众所周知的方式在特定位置切割DNA。这些化合物将有助于DNA损伤的基础研究，也将被应用于基因组测序和光疗。利用光科学作为跨学科的统一论坛，对本科高级实验室课程和研究生课程进行探究性课程修改。组织了一次化学和生物科学的区域本科生研究专题讨论会，这将帮助参加讨论会的学生为工业职业和高级研究生培训做好准备。

This CAREER award in the Inorganic, Bioinorganic and Organometallic Chemistry program supports research on the design, synthesis and study of a series of imide chromophores to photochemically cleave DNA, by Professor Lisa Kelly of the Department of Chemistry and Biochemistry at the University of Maryland-Baltimore County. Thymidine sites will be targeted and cleavage of guanine will be measured. The photosensitizers will be recycled in the presence of oxygen and double stranded nucleic acid cleavage will be possible. Macrocycles will be covalently attached to the chromophores and a variety of metal ions coordinated to them. These metal ions will include Zn(II) (pyrimidine-specific), Cd(II) and Pb(II) (heavy atoms), and Co(III) and Cu(II) (electron acceptors). By use of these metal complexes the effect of site-targeting, increased excited state triplet yield, and electron-hole separation after photoactivation will be determined. These investigations will provide information on the mechanism of oxidative damage in nucleic acid polymers, specifically on the relationship between the initial site of redox reactivity and the final site of cleavage.The goal of this research is to develop optimized photoactive compounds which can be used to cleave DNA at specific sites in a well-understood manner. These compounds will be useful for fundamental studies of DNA damage and also find application to genomic sequencing and phototherapy. Using the photosciences as a cross-disciplinary unified forum, inquiry-based curricular revisions will be made to both the undergraduate advanced laboratory and graduate courses. A regional undergraduate research symposium in the chemical and biological sciences has been organized which will help prepare the participating students for careers in industry as well as for advanced graduate training.