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Published on: May 12, 2023
Colchicine selective interaction with oncogene RET G-quadruplex revealed by NMR
Fei Wang1, Chunxi Wang1, Yaping Liu1
1State Key Laboratory of Bioorganic and Natural Product Chemistry, Center for Excellence in Molecular Synthesis, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 345 Lingling Road, Shanghai, 200032, China. ccao@mail.sioc.ac.cn and University of Chinese Academy of Science, No. 19A, Yuquan Road, Shijingshan District, Beijing, 100049, China.
Colchicine selectively binds to the RET oncogene G-quadruplex (G4) DNA. This discovery offers a potential new strategy for developing targeted anticancer therapies against specific G4 structures.
Area of Science:
- Biochemistry
- Molecular Biology
- Medicinal Chemistry
Background:
- G-quadruplexes (G4s) are DNA structures found in oncogene promoter regions.
- These G4 structures are promising targets for anticancer drug development.
- Selective G4 ligand discovery is challenging due to structural similarities.
Purpose of the Study:
- To investigate the selective binding of small molecules to specific G-quadruplex DNA structures.
- To identify potential drug candidates for targeting oncogenes via G4 interactions.
Main Methods:
- Nuclear Magnetic Resonance (NMR) spectroscopy was the primary technique used.
- Structural analysis of G-quadruplex DNA and ligand interactions.
Main Results:
- Colchicine was found to selectively bind to the G-quadruplex DNA of the RET oncogene.
- This selective interaction was confirmed using NMR spectroscopy.
Conclusions:
- Colchicine exhibits specific binding to the RET oncogene G-quadruplex.
- This selectivity provides a foundation for developing targeted therapies against RET-driven cancers.
