6S15

Pyridine derivative of the natural alkaloid Berberine as Human Telomeric G-quadruplex Binder

Summary for 6S15

• Entry DOI: 10.2210/pdb6s15/pdb
• Descriptor: DNA TAGGGTTAGGGT, POTASSIUM ION, Berberine, ... (4 entities in total)
• Functional Keywords: drug-dna complex, telomeric g-quadruplex, dna
• Biological source: synthetic construct
• Total number of polymer chains: 2
• Total formula weight: 8080.64

Authors

Ferraroni, M.,Bazzicalupi, C.,Gratteri, P.,Papi, F. (deposition date: 2019-06-18, release date: 2020-06-03, Last modification date: 2024-01-24)

Primary citation

Papi, F.,Bazzicalupi, C.,Ferraroni, M.,Ciolli, G.,Lombardi, P.,Khan, A.Y.,Kumar, G.S.,Gratteri, P.
Pyridine Derivative of the Natural Alkaloid Berberine as Human Telomeric G4-DNA Binder: A Solution and Solid-State Study.
Acs Med.Chem.Lett., 11:645-650, 2020

PubMed Abstract: Telomerase is an enzyme deputed to the maintenance of eukaryotic chromosomes; however, its overexpression is a recognized hallmark of many cancer forms. A viable route for the inhibition of telomerase in malignant cells is the stabilization of G-quadruplex structures (G) at the 3' overhang of telomeres. Berberine has shown in this regard valuable G binding properties together with a significant anticancer activity and telomerase inhibition effects. Here, we focused on a berberine derivative featuring a pyridine containing side group at the 13th position. Such modification actually improves the binding toward telomeric G-quadruplexes and establishes a degree of selectivity in the interaction with different sequences. Moreover, the X-ray crystal structure obtained for the complex formed by the ligand and a bimolecular human telomeric quadruplex affords a better understanding of the 13-berberine derivatives behavior with telomeric G and allows to draw useful insights for the future design of derivatives with remarkable anticancer properties.

PubMed: 32435365
DOI: 10.1021/acsmedchemlett.9b00516

Experimental method

X-RAY DIFFRACTION (1.7 Å)