title: Synthesis and biological evaluation of a novel pentagastrin-toxin conjugate designed for a targeted prodrug mono-therapy of cancer.
abstract: A novel carbamate prodrug 2 containing a pentagastrin moiety was synthesized. 2 was designed as a detoxified analogue of the highly cytotoxic natural antibiotic duocarmycin SA (1) for the use in a targeted prodrug monotherapy of cancers expressing cholecystokinin (CCK-B)/gastrin receptors. The synthesis of prodrug 2 was performed using a palladium-catalyzed carbonylation of bromide 6, followed by a radical cyclisation to give the pharmacophoric unit 10, coupling of 10 to the DNA-binding subunit 15 and transformation of the resulting seco-drug 3b into the carbamate 2 via addition of a pentagastrin moiety.
authors.affiliation: Institute of Organic and Biomolecular Chemistry, Georg-August-University Göttingen, Tammannstraße 2, D-37077 Göttingen, Germany.
authors.forename: Lutz F
authors.initials: LF
authors.lastname: Tietze
authors.affiliation: Institute of Organic and Biomolecular Chemistry, Georg-August-University Göttingen, Tammannstraße 2, D-37077 Göttingen, Germany.
authors.forename: Olaf
authors.initials: O
authors.lastname: Panknin
authors.affiliation: Institute of Organic and Biomolecular Chemistry, Georg-August-University Göttingen, Tammannstraße 2, D-37077 Göttingen, Germany.
authors.forename: Birgit
authors.initials: B
authors.lastname: Krewer
authors.affiliation: Institute of Organic and Biomolecular Chemistry, Georg-August-University Göttingen, Tammannstraße 2, D-37077 Göttingen, Germany.
authors.forename: Felix
authors.initials: F
authors.lastname: Major
authors.affiliation: Institute of Organic and Biomolecular Chemistry, Georg-August-University Göttingen, Tammannstraße 2, D-37077 Göttingen, Germany.
authors.forename: Ingrid
authors.initials: I
authors.lastname: Schuberth