Targeting duplex DNA with the reversible reactivity of quinone methides

作     者：Chengyun Huang Yang Liu Steven E Rokita 

作者机构：Department of Chemistry and BiochemistryUniversity of MarylandCollege ParkMDUSA Chengdu Integrated Testing Center of Rocks and OresChengduSichuanChina National Institutes for Food and Drug ControlBeijingChina Department of ChemistryJohns Hopkins UniversityBaltimoreMDUSA. 

出 版 物：《Signal Transduction and Targeted Therapy》 (信号转导与靶向治疗（英文）)

年 卷 期：2016年第1卷第1期

页      面：101-105页

核心收录：

学科分类：0710[理学-生物学] 1002[医学-临床医学] 081704[工学-应用化学] 1001[医学-基础医学(可授医学、理学学位)] 07[理学] 08[工学] 0817[工学-化学工程与技术] 070303[理学-有机化学] 0703[理学-化学] 

基　　金：support from the NSF(CHE-1405123) prior support from the NIH(CA81571) 

主　　题：reversible alkylation reactivity 

摘      要：DNA alkylation and crosslinking remains a common and effective strategy for anticancer chemotherapy despite its infamous lack of *** a reactive group to a sequence-directing component has the potential to enhance target selectivity but may suffer from premature degradation or the need for an external signal for ***,quinone methide conjugates may be employed if they form covalent but reversible adducts with their sequence directing *** resulting self-adducts transfer their quinone methide to a chosen target without an external signal and avoid off-target reactions by alternative intramolecular *** transfer is shown to depend on the nature of the quinone methide and the sequencedirecting ligand in applications involving alkylation of duplex DNA through a triplex recognition *** required an electron-rich derivative that enhanced the stability of the transient quinone methide intermediate and a polypyrimidine strand of DNA to associate with its cognate polypurine/polypyrimidine *** quinone methide conjugates with peptide nucleic acids were capable of quinone methide transfer from their initial precursor but not from their corresponding *** active peptide nucleic acid derivatives were highly selective for their complementary target.