Enhanced Recognition of a Herbal Compound Epiberberine by a DNA Quadruplex-Duplex Structure.

Autor: Zhan X; School of Medicine, The Chinese University of Hong Kong, Shenzhen (CUHK-Shenzhen), Shenzhen 518172, Guangdong, P. R. China., Deng L; School of Medicine, The Chinese University of Hong Kong, Shenzhen (CUHK-Shenzhen), Shenzhen 518172, Guangdong, P. R. China., Lian Y; School of Medicine, The Chinese University of Hong Kong, Shenzhen (CUHK-Shenzhen), Shenzhen 518172, Guangdong, P. R. China., Shu Z; Division of Chemistry and Biological Chemistry, School of Physical and Mathematical Sciences, Nanyang Technological University, 637371 Singapore., Xu Y; School of Medicine, The Chinese University of Hong Kong, Shenzhen (CUHK-Shenzhen), Shenzhen 518172, Guangdong, P. R. China., Mai X; School of Medicine, The Chinese University of Hong Kong, Shenzhen (CUHK-Shenzhen), Shenzhen 518172, Guangdong, P. R. China., Krishna MS; Division of Chemistry and Biological Chemistry, School of Physical and Mathematical Sciences, Nanyang Technological University, 637371 Singapore., Lu R; School of Medicine, The Chinese University of Hong Kong, Shenzhen (CUHK-Shenzhen), Shenzhen 518172, Guangdong, P. R. China., Wang A; School of Medicine, The Chinese University of Hong Kong, Shenzhen (CUHK-Shenzhen), Shenzhen 518172, Guangdong, P. R. China., Bai S; School of Medicine, The Chinese University of Hong Kong, Shenzhen (CUHK-Shenzhen), Shenzhen 518172, Guangdong, P. R. China., Zhou F; School of Medicine, The Chinese University of Hong Kong, Shenzhen (CUHK-Shenzhen), Shenzhen 518172, Guangdong, P. R. China., Xiong C; MinJiang Collaborative Center for Theoretical Physics, College of Physics and Electronic Information Engineering, Minjiang University, Fuzhou 350108, Fujian, P. R. China., Xu Y; LightEdge Technologies Ltd., Zhongshan 528400, Guangdong, P. R. China., Ni J; School of Medicine, The Chinese University of Hong Kong, Shenzhen (CUHK-Shenzhen), Shenzhen 518172, Guangdong, P. R. China., Vandana JJ; Department of Surgery, Weill Cornell Medicine, New York, New York 10065, United States.; Tri-Institutional PhD Program in Chemical Biology, Weill Cornell Medicine, Memorial Sloan Kettering Cancer Center, The Rockefeller University, New York, New York 10065, United States., Wang Z; School of Medicine, The Chinese University of Hong Kong, Shenzhen (CUHK-Shenzhen), Shenzhen 518172, Guangdong, P. R. China., Li Y; Department of Urology, South China Hospital of Shenzhen University, Shenzhen 518111, Guangdong, P. R. China., Sun D; Guangdong Yifang Pharmaceutical, Foshan 528244, Guangdong, P. R. China., Huang S; School of Life Sciences, University of Chinese Academy of Sciences, Beijing 101499, P. R. China., Liu J; School of Medicine, The Second Affiliated Hospital, The Chinese University of Hong Kong, Shenzhen 518172, Guangdong, P. R. China., Cheng GJ; School of Medicine, The Chinese University of Hong Kong, Shenzhen (CUHK-Shenzhen), Shenzhen 518172, Guangdong, P. R. China., Wu S; Department of Urology, South China Hospital of Shenzhen University, Shenzhen 518111, Guangdong, P. R. China., Chiang YC; School of Medicine, The Chinese University of Hong Kong, Shenzhen (CUHK-Shenzhen), Shenzhen 518172, Guangdong, P. R. China., Stjepanovic G; School of Medicine, The Chinese University of Hong Kong, Shenzhen (CUHK-Shenzhen), Shenzhen 518172, Guangdong, P. R. China., Jiang C; School of Medicine, The Chinese University of Hong Kong, Shenzhen (CUHK-Shenzhen), Shenzhen 518172, Guangdong, P. R. China., Shao Y; Key Laboratory of the Ministry of Education for Advanced Catalysis Materials, College of Chemistry and Materials Science, Zhejiang Normal University, Jinhua 321004, Zhejiang, P. R. China., Chen G; School of Medicine, The Chinese University of Hong Kong, Shenzhen (CUHK-Shenzhen), Shenzhen 518172, Guangdong, P. R. China.; Shenzhen Key Laboratory of Innovative Drug Synthesis, The Chinese University of Hong Kong, Shenzhen 518172, P. R. China.
Jazyk: angličtina
Zdroj: Analytical chemistry [Anal Chem] 2024 Aug 13; Vol. 96 (32), pp. 13174-13184. Date of Electronic Publication: 2024 Aug 02.
DOI: 10.1021/acs.analchem.4c02054
Abstrakt: The small molecule epiberberine (EPI) is a natural alkaloid with versatile bioactivities against several diseases including cancer and bacterial infection. EPI can induce the formation of a unique binding pocket at the 5' side of a human telomeric G-quadruplex (HTG) sequence with four telomeric repeats (Q4), resulting in a nanomolar binding affinity ( K D approximately 26 nM) with significant fluorescence enhancement upon binding. It is important to understand (1) how EPI binding affects HTG structural stability and (2) how enhanced EPI binding may be achieved through the engineering of the DNA binding pocket. In this work, the EPI-binding-induced HTG structure stabilization effect was probed by a peptide nucleic acid (PNA) invasion assay in combination with a series of biophysical techniques. We show that the PNA invasion-based method may be useful for the characterization of compounds binding to DNA (and RNA) structures under physiological conditions without the need to vary the solution temperature or buffer components, which are typically needed for structural stability characterization. Importantly, the combination of theoretical modeling and experimental quantification allows us to successfully engineer Q4 derivative Q4-ds-A by a simple extension of a duplex structure to Q4 at the 5' end. Q4-ds-A is an excellent EPI binder with a K D of 8 nM, with the binding enhancement achieved through the preformation of a binding pocket and a reduced dissociation rate. The tight binding of Q4 and Q4-ds-A with EPI allows us to develop a novel magnetic bead-based affinity purification system to effectively extract EPI from Rhizoma coptidis (Huang Lian) extracts.
Databáze: MEDLINE
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