Kinase-mediated trapping of bi-functional conjugates of paclitaxel or vinblastine with thymidine in cancer cells
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- 作者：Simon E. Aspland ; Carlo Ballatore ; Rosario Castillo ; Joel Desharnais ; Trisha Eustaquio ; Philip Goelet ; Zijian Guo ; Qing Li ; David Nelson ; Chengzao Sun et al.
- 关键词：Kinase-mediated trapping ; Thymidine kinase 1 ; Thymidine ; Paclitaxel ; Vinblastine ; Fluorescein
- 刊名：Bioorganic and Medicinal Chemistry Letters
- 出版年：2006
- 出版时间：1 October 2006
- 年：2006
- 卷：16
- 期：19
- 页码：5194-5198
- 全文大小：171 K
文摘
In the present work, we explore the possibility of introducing selectivity to existing chemotherapeutics via the design of non-pro-drug, bi-functional molecules comprising a microtubule-binding agent and a substrate for a disease-associated kinase. The design, synthesis, and in vitro biological evaluation of paclitaxel–thymidine and vinblastine–thymidine bi-functional conjugates are reported here. This work provides the first account of ‘kinase-mediated trapping’ of cancer therapeutics.