Foley Corinne N, Chen Liang-An, Sackett Dan L, Leighton James L
Department of Chemistry, Columbia University, New York, New York 10027, United States.
Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892, United States.
ACS Med Chem Lett. 2017 May 1;8(7):701-704. doi: 10.1021/acsmedchemlett.7b00131. eCollection 2017 Jul 13.
An approach to the validation of a linker strategy for the epothilone family of microtubule-stabilizing agents is reported. An analogue of epothilone B in which the C(6) methyl group has been replaced with a 4-azidobutyl group has been prepared by total chemical synthesis, and amides derived from the azido group have been shown to retain the activity of the parent compound. These results set the stage for an evaluation of the potential of the epothilones to serve as the drug component of antibody-drug conjugates and other selective tumor cell-targeting conjugates.
报道了一种用于验证埃坡霉素家族微管稳定剂连接策略的方法。通过全化学合成制备了埃坡霉素B的类似物,其中C(6)甲基已被4-叠氮基丁基取代,并且已证明源自叠氮基的酰胺保留了母体化合物的活性。这些结果为评估埃坡霉素作为抗体-药物偶联物和其他选择性肿瘤细胞靶向偶联物的药物成分的潜力奠定了基础。