title: Preparation of new alkyne-modified ansamitocins by mutasynthesis.
abstract: The preparation of alkyne-modified ansamitocins by mutasynthetic supplementation of Actinosynnema pretiosum mutants with alkyne-substituted aminobenzoic acids is described. This modification paved the way to introduce a thiol linker by Huisgen-type cycloaddition which can principally be utilized to create tumor targeting conjugates. In bioactivity tests, only those new ansamitocin derivatives showed strong antiproliferative activity that bear an ester side chain at C-3.
authors.affiliation: Institute of Organic Chemistry and Center of Biomolecular Drug Research (BMWZ), Leibniz University Hannover, Schneiderberg 1b, 30167 Hannover, Germany.
authors.forename: Kirsten
authors.initials: K
authors.lastname: Harmrolfs
authors.affiliation: Institute of Organic Chemistry and Center of Biomolecular Drug Research (BMWZ), Leibniz University Hannover, Schneiderberg 1b, 30167 Hannover, Germany.
authors.forename: Lena
authors.initials: L
authors.lastname: Mancuso
authors.affiliation: Institute of Organic Chemistry and Center of Biomolecular Drug Research (BMWZ), Leibniz University Hannover, Schneiderberg 1b, 30167 Hannover, Germany.
authors.forename: Binia
authors.initials: B
authors.lastname: Drung
authors.affiliation: Department of Chemical Biology, Helmholtz Center for Infectious Research (HZI), Inhoffenstraße 7, D-38124 Braunschweig, Germany.
authors.forename: Florenz
authors.initials: F
authors.lastname: Sasse
authors.affiliation: Institute of Organic Chemistry and Center of Biomolecular Drug Research (BMWZ), Leibniz University Hannover, Schneiderberg 1b, 30167 Hannover, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Kirschning
keywords: ansamitocins; antibiotics; antitumor agents; click chemistry; mutasynthesis; natural products