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The Two Faces of Potent Antitumor Duocarmycin‐Based Drugs: A Structural Dissection Reveals Disparate Motifs for DNA versus Aldehyde Dehydrogenase 1 Affinity
Author(s) -
Wirth Tanja,
Pestel Galina F.,
Ganal Vanessa,
Kirmeier Thomas,
Schuberth Ingrid,
Rein Theo,
Tietze Professor Lutz F.,
Sieber Professor Stephan A.
Publication year - 2013
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.201208941
Subject(s) - moiety , aldehyde dehydrogenase , dna , chemistry , aldehyde , computational biology , stereochemistry , combinatorial chemistry , biochemistry , computer science , gene , biology , catalysis
Duocarmycin‐derived seco‐cyclopropabenzindole (CBI) drugs have been shown to bind DNA and an aldehyde dehydrogenase (ALDH1A1) in lung cancer cells. The removal of the DNA‐binding indole moiety results in a CBI compound that does not bind to DNA in whole cells but still exhibits remarkable cytotoxicity. This CBI compound has an increased affinity for ALDH1A1. Rh=rhodamine.