Preparation of thermocleavable conjugates based on ansamitocin and superparamagnetic nanostructured particles by a chemobiosynthetic approach

verfasst von

Lena Mancuso, Tobias Knobloch, Jessica Buchholz, Jan Hartwig, Lena Möller, Katja Seidel, Wera Collisi, Florenz Sasse, Andreas Kirschning

Abstract

A combination of mutasynthesis, precursor-directed biosynthesis and semisynthesis provides access to new ansamitocin derivatives including new nanostructured particle-drug conjugates. These conjugates are based on the toxin ansamitocin and superparamagnetic iron oxide-silica core shell particles. New ansamitocin derivatives that are functionalized either with alkynylor azido groups in the ester side chain at C-3 are attached to nanostructured iron oxide core-silica shell particles. Upon exposure to an oscillating electromagnetic field these conjugates heat up and the ansamitocin derivatives are released by a retro-Diels-Alder reaction. For example, one ansamitocin derivative exerts strong antiproliferative activity against various cancer cell lines in the lower nanomolar range while the corresponding nanostructured particle-drug conjugate is not toxic. Therefore, these new conjugates can serve as dormant toxins that can be employed simultaneously in hyperthermia and chemotherapy when external inductive heating is applied.

Organisationseinheit(en)

Institut für Organische Chemie
Zentrum für Biomolekulare Wirkstoffe (BMWZ)

Externe Organisation(en)

Helmholtz-Zentrum für Infektionsforschung GmbH (HZI)

Typ

Artikel

Journal

Chemistry - A European Journal

Band

20

Seiten

17541-17551

Anzahl der Seiten

11

ISSN

0947-6539

Publikationsdatum

24.10.2014

Publikationsstatus

Veröffentlicht

Peer-reviewed

Ja

ASJC Scopus Sachgebiete

Katalyse, Organische Chemie

Ziele für nachhaltige Entwicklung

SDG 3 – Gute Gesundheit und Wohlergehen

Elektronische Version(en)

https://doi.org/10.1002/chem.201404502 (Zugang: Geschlossen)