2023年11月14日星期二 美国约翰霍普金斯大学Steven Rokita教授报告

主题：Ligand-Controlled Modification of DNA with a Dynamic and Transient Electrophilic Intermediate

活动时间：2023年11月14日周二下午16:00

活动地址：东校园化学与材料综合楼B407-409

主讲人：Steven Rokita 教授 美国约翰霍普金斯大学

主持人：徐 亮 教授

报告摘要：

The vast majority of drugs designed to interact covalently with nucleic acids react irreversibly and stoichiometrically.  Once the resulting lesions are repaired, their biological impact is minimal.  In contrast, a reversible reagent has the potential to support a continuum of reoccurring reactions despite lesion repair.  The potential utility for such a strategy will be tested after optimizing quinone methide alkylation and regeneration.  This intermediate is sufficiently promiscuous to act under control of its attached ligand and may be designed for either alkylation and cross-linking of various nucleic acid targets.  For example, an acridine conjugate directs modification to the highly nucleophilic guanine N7 of the major groove in B-helical DNA while a polyamine conjugate directs modification to the weakly nucleophilic sites within the corresponding minor groove.  The mobility and efficiency of cross-linking is also dependent on the choice of intercalator linked to the quinone methide as evident by the contrasting dynamics of derivatives based on acridine versus naphthalimide.  Subtle changes in the linker used for conjugation also have a significant impact on reaction site and efficiency.  Results to date suggest that specificity can be built into the linker as well as the intercalator.

报告人简介：

Steven E. Rokita教授，1979年本科毕业于加州大学伯克利分校化学学院，1983年博士毕业于麻省理工学院化学系。Rokita教授先后在University at Stony Brook和University of Maryland担任助理教授、副教授和教授等职位；2012年，加入Johns Hopkins University（约翰霍普金斯大学），成为化学系和生物系的联合教授，并担任化学与生物交叉的研究生培训项目主任。2011年，当选为美国科学促进会院士。Rokita教授在生物有机和生物无机化学，核酸化学和酶学等领域具有广泛的研究兴趣。