A Bio-Chemosynthetic Approach to Superparamagnetic Iron Oxide-Ansamitocin Conjugates for Use in Magnetic Drug Targeting
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- 作者：Dr. Liang-Liang Wang ; Dr. Asha Balakrishnan ; Dr. Nadja-Carola Bigall ; Dr. David Candito ; Jan Frederick Miethe ; Katja Seidel ; Yu Xie ; Prof. Dr. Michael Ott and Prof. Dr. Andreas Kirschning
- 刊名：Chemistry - A European Journal
- 出版年：2017
- 出版时间：February 16, 2017
- 年：2017
- 卷：23
- 期：10
- 页码：2265-2270
- 全文大小：1140K
- ISSN：1521-3765
文摘
A combination of mutasynthesis using a mutant strain of A. pretiosum blocked in the biosynthesis of amino-hydroxybenzoic acid (AHBA) and semisynthesis relying on a Stille cross-coupling step provided access to new ansamitocin derivatives of which one was attached by a thermolabile linker to nanostructured iron oxide particles. When exposed to an oscillating electromagnetic field the resulting iron oxide/ansamitocin conjugate 19 heats up in an aqueous suspension and the ansamitocin derivative 16 is released by means of a retro-Diels–Alder reaction. It exerts strong antiproliferative activity (IC50=4.8 ng mg−1) in mouse fibroblasts. These new types of conjugates have the potential for combating cancer through hyperthermia and chemotherapy using an electromagnetic external trigger.