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

authored by

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.

Organisation(s)

Institute of Organic Chemistry
Centre of Biomolecular Drug Research (BMWZ)

External Organisation(s)

Helmholtz Centre for Infection Research (HZI)

Type

Article

Journal

Chemistry - A European Journal

Volume

20

Pages

17541-17551

No. of pages

11

ISSN

0947-6539

Publication date

24.10.2014

Publication status

Published

Peer reviewed

Yes

ASJC Scopus subject areas

Catalysis, Organic Chemistry

Sustainable Development Goals

SDG 3 - Good Health and Well-being

Electronic version(s)

https://doi.org/10.1002/chem.201404502 (Access: Closed)