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Updated: May 21, 2026
In Vitro Chemical Mapping of G-Quadruplex DNA Structures by Bis-3-Chloropiperidines
Published on: May 12, 2023
Crystal Structure of Trabectedin-DNA Complex
Caixia Hou1, Nishad Thamban Chandrika1, Markos Leggas2
1Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, 789 S. Limestone St., Lexington, KY 40536, USA.
None:
Trabectedin is a DNA-binding natural product with potent anticancer activities. Trabectedin is used clinically worldwide to treat soft tissue sarcomas and ovarian cancer. A crystal structure of trabectedin in complex with DNA has been elusive. This study describes a crystal structure of a covalent trabectedin-DNA complex at a resolution of 1.8 Å. The structure demonstrates the conformation and position of the trabectedin adduct in the minor groove of DNA, revealing numerous drug-DNA interactions, conformational differences in DNA and trabectedin caused by their binding. The structure also explains the previously observed DNA sequence preference of trabectedin. This crystal structure will be useful for further inquiry into the mechanism of action of trabectedin and for the rational design of improved trabectedin analogues.
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