title: A Bio-Chemosynthetic Approach to Superparamagnetic Iron Oxide-Ansamitocin Conjugates for Use in Magnetic Drug Targeting.
abstract: 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.
authors.affiliation: Institut für Organische Chemie und Biomolekulares Wirkstoffzentrum (BMWZ), Leibniz Universität Hannover, Schneiderberg 1B, 30167, Hannover, Germany.
authors.forename: Liang-Liang
authors.initials: LL
authors.lastname: Wang
authors.affiliation: Department of Gastroenterology, Hepatology, and Endocrinology, Hannover Medical School (MHH), TWINCORE, Center for Experimental and Clinical Infection Research, Feodor-Lynen-Str. 7, 30625, Hannover, Germany.
authors.forename: Asha
authors.initials: A
authors.lastname: Balakrishnan
authors.affiliation: Institut für Physikalische Chemie und Elektrochemie, Leibniz Universität Hannover, Callinstr. 3A, 30167, Hannover, Germany.
authors.forename: Nadja-Carola
authors.initials: NC
authors.lastname: Bigall
authors.affiliation: Institut für Organische Chemie und Biomolekulares Wirkstoffzentrum (BMWZ), Leibniz Universität Hannover, Schneiderberg 1B, 30167, Hannover, Germany.
authors.forename: David
authors.initials: D
authors.lastname: Candito
authors.affiliation: Institut für Physikalische Chemie und Elektrochemie, Leibniz Universität Hannover, Callinstr. 3A, 30167, Hannover, Germany.
authors.forename: Jan Frederick
authors.initials: JF
authors.lastname: Miethe
authors.affiliation: Institut für Organische Chemie und Biomolekulares Wirkstoffzentrum (BMWZ), Leibniz Universität Hannover, Schneiderberg 1B, 30167, Hannover, Germany.
authors.forename: Katja
authors.initials: K
authors.lastname: Seidel
authors.affiliation: Department of Gastroenterology, Hepatology, and Endocrinology, Hannover Medical School (MHH), TWINCORE, Center for Experimental and Clinical Infection Research, Feodor-Lynen-Str. 7, 30625, Hannover, Germany.
authors.forename: Yu
authors.initials: Y
authors.lastname: Xie
authors.affiliation: Department of Gastroenterology, Hepatology, and Endocrinology, Hannover Medical School (MHH), TWINCORE, Center for Experimental and Clinical Infection Research, Feodor-Lynen-Str. 7, 30625, Hannover, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Ott
authors.affiliation: Institut für Organische Chemie und Biomolekulares Wirkstoffzentrum (BMWZ), Leibniz Universität Hannover, Schneiderberg 1B, 30167, Hannover, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Kirschning
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D061565:Cycloaddition Reaction; D005290:Ferric Compounds / Q000737:chemistry*; D062385:Hydroxybenzoates / Q000138:chemical synthesis / Q000737:chemistry / Q000633:toxicity; D058185:Magnetite Nanoparticles / Q000737:chemistry* / Q000633:toxicity; D008453:Maytansine / Q000031:analogs & derivatives* / Q000737:chemistry; D051379:Mice
chemical_list: D005290:Ferric Compounds; D062385:Hydroxybenzoates; D058185:Magnetite Nanoparticles; D008453:Maytansine; C000499:ferric oxide; C015682:ansamitocins
keywords: Diels-Alder reaction; ansamitocin; chemotherapy; drug delivery; hyperthermia; nanoparticles