DSSR-derived G-quadruplex features in PDB entry 6s15
Poster "DSSR-Enabled Automatic Identification and Annotation of G-quadruplexes in the PDB" presented at the RNA2020 online meeting
Citation: before a paper dedicated to the DSSR-G4 module comes out, please cite the 2015 DSSR paper published in Nucleic Acids Research.
- X-ray (1.7 Å)
- Pyridine derivative of the natural alkaloid berberine as human telomeric G-quadruplex binder
- Papi, F., Bazzicalupi, C., Ferraroni, M., Ciolli, G., Lombardi, P., Khan, A.Y., Kumar, G.S., Gratteri, P.: (2020) "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.
- 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 (G4) at the 3' overhang of telomeres. Berberine has shown in this regard valuable G4 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 G4 and allows to draw useful insights for the future design of derivatives with remarkable anticancer properties.
- G4 notes
- 3 G-tetrads, 1 G4 helix, 1 G4 stem · parallel(4+0), UUUU
1 glyco-bond=---- groove=---- planarity=0.109 type=planar nts=4 GGGG A.DG3,A.DG9,B.DG15,B.DG21 2 glyco-bond=---- groove=---- planarity=0.144 type=planar nts=4 GGGG A.DG4,A.DG10,B.DG16,B.DG22 3 glyco-bond=---- groove=---- planarity=0.306 type=bowl nts=4 GGGG A.DG5,A.DG11,B.DG17,B.DG23