Phthalocyanines for G-quadruplex aptamers binding

0531068 - BFÚ 2021 RIV US eng J - Journal Article
Lopes-Nunes, J. - Carvalho, J. - Figueiredo, J. - Ramos, C. I. V. - Lourenco, L. M. O. - Tome, J. P. C. - Neves, M. G. P. M. S. - Mergny, Jean-Louis - Queiroz, J.A. - Salgado, G. F. - Cruz, C.
Phthalocyanines for G-quadruplex aptamers binding.
Bioorganic Chemistry. Roč. 100, JUL 2020 (2020), č. článku 103920. ISSN 0045-2068. E-ISSN 1090-2120
R&D Projects: GA MŠMT EF15_003/0000477
Institutional support: RVO:68081707
Keywords : dna * telomerase * derivatives
OECD category: Biochemistry and molecular biology
Impact factor: 5.275, year: 2020
Method of publishing: Limited access
https://www.sciencedirect.com/science/article/pii/S0045206820302194?via%3Dihub

The G-quadruplex (G4)-forming sequence within the AS1411 derivatives with alternative nucleobases and backbones can improve the chemical and biological properties of AS1411. Zn(II) phthalocyanine (ZnPc) derivatives have potential as high-affinity G4 ligands because they have similar size and shape to the G-quartets.

The interactions of four Zn(II) phthalocyanines with the G4 AS1411 aptamer and its derivatives were determined by biophysical techniques, molecular docking and gel electrophoresis. Cell viability assay was carried out to evaluate the antiproliferative effects of Zn(II) phthalocyanines and complexes.

CD experiments showed structural changes after addition of ZnPc 4, consistent with multiple binding modes and conformations shown by NMR and gel electrophoresis. CD melting confirmed that ZnPc 2 and ZnPc 4, both containing eight positive charges, are able to stabilize the AT11 G4 structure (ΔTm > 30 °C and 18.5 °C, respectively). Molecular docking studies of ZnPc 3 and ZnPc 4 suggested a preferential binding to the 3′- and 5′-end, respectively, of the AT11 G4. ZnPc 3 and its AT11 and AT11-L0 complexes revealed pronounced cytotoxic effect against cervical cancer cells and no cytotoxicity to normal human cells.

Zn(II) phthalocyanines provide the basis for the development of effective therapeutic agents as G4 ligands.
Permanent Link: http://hdl.handle.net/11104/0309818