Existence of G-quadruplex structures in promoter region of oncogenes confirmed by G-quadruplex DNA cross-linking strategy

Abstract

Existence of G-quadruplex DNA in vivo always attract widespread interest in the field of biology and biological chemistry. We reported our findings for the existence of G-quadruplex structures in promoter region of oncogenes confirmed by G-quadruplex DNA cross-linking strategy. Probes for selective G-quadruplex cross-linking was designed and synthesized that show high selectivity for G-quadruplex cross-linking. Further biological studies demonstrated its good inhibition activity against murine melanoma cells. To further investigate if G-quadruplex DNA was formed in vivo and as the target, a derivative was synthesized and pull-down process toward chromosome DNAs combined with circular dichroism and high throughput deep sequencing were performed. Several simulated intracellular conditions, including X. laevis oocytes, Ficoll 70 and PEG, was used to investigate the compound's pure cross-linking ability upon preformed G-quadruplex. Thus, as a potent G-quadruplex cross-linking agent, our strategy provided both valuable evidence of G-quadruplex structures in vivo and intense potential in anti-cancer therapy.

Targeting human telomeric G-quadruplex DNA with antitumour natural alkaloid aristololactam-β-D-glucoside and its comparison with daunomycin

“…The formation and stabilization of this structure are further dependent on the presence of a monovalent cation, especially potassium and sodium, which sits in a central channel between each pair of tetrads . DNA sequences that can form G‐quadruplexes are widely present in biologically relevant regions of genes contributing to genomic stability, control of replication, and gene expression . The first biologically relevant quadruplex forming sequences were discovered in eukaryotic chromosomal telomeric DNA .…”

“…1,2 DNA sequences that can form G-quadruplexes are widely present in biologically relevant regions of genes contributing to genomic stability, control of replication, and gene expression. [3][4][5][6] The first biologically relevant quadruplex forming sequences were discovered in eukaryotic chromosomal telomeric DNA. 3,4,6 The telomere region contains d(TTAGGG) tandom sequences, which can fold spontaneously into G-quadruplex structures.…”

Preparation of 6/8/11-Amino/Chloro-Oxoisoaporphine and Group-10 Metal Complexes and Evaluation of Their in Vitro and in Vivo Antitumor Activity

“…However, the CD spectrum Pu27 G4 in the presence of complexes 1 – 3 suggested a mixture G-quadruplexes DNA of parallel and antiparallel G-quadruplex conformations, likely because 1 – 3 preferentially folded the Pu27 G4 DNA into a mixed-type or hybrid G4 structure in these experimental conditions5152. In all, it is clear that the parallel and antiparallel (mixed-type or hybrid G4 structure) conformation of the G4 DNA after treatment with 1 – 3 was favorable for the binding of Pu27 G4 in TBS, which also suggested that complexes 1 – 3 might interact with the loops and grooves of G-quadruplex DNA102433385152. In addition, in the presence of K + , the CD data indicated that HTG21, and Pu39 DNAs (sequence) exhibited a mixture G-quadruplex DNA in parallel and antiparallel G-quadruplex conformations24385152, similar to 1 – 3 treated Pu27 G4 (Figs S78–S80 and Table S10).…”

“…Comparison of the ESI-MS spectra before and after complex treated showed that 3 was coordinated to the guanine of G4-DNA (Fig. S77), whereas 6 and 10 might have been interacting with the π-π stacking of the G-quadruplex1033. FID and ESI-MS spectra experiments showed that the organometallic platinum(II) complexes 7 and 10 with a direct metal-carbon bond offers different possibilities for exploration as anticancer agents due to the large structural differentiation between the different ligands (e.g.…”

“…They differ from other nucleic acid secondary structures and are often associated with human diseases like cancer1, HIV2, and diabetes3, which make the G-quadruplex a potential therapeutic target. Recently, a variety of G4s, such as c-myc, c-kit-2, bcl-2, POT1, and c-kit-1, is considered as an appealing opportunity for drugs or compounds intervention in anticancer therapy45678910.…”