We report the NMR solution structure of the intramolecular G-quadruplex formed in human telomeric DNA in K(+). The hybrid-type telomeric G-quadruplex consists of three G-tetrads linked with mixed parallel-antiparallel G-strands, with the bottom two G-tetrads having the same G-arrangement (anti:anti:syn:anti) and the top G-tetrad having the reversed G-arrangement (syn:syn:anti:syn). The three TT...

Bis-indolinone derivatives having either 2,6-disubstituted pyridine core (1a and 1b) or 1,10-disubstituted phenanthroline core (2a and 2b), already known to have antitumor activity, have been tested as potential G-quadruplex binders. Compounds 2a and 2b are able to selectively stabilize G-quadruplex over duplex DNA, and also to discriminate among different G-quadruplex structures, having a part...

A series of luminescent Ir(III) complexes were synthesised and evaluated for their ability to act as luminescent G-quadruplex-selective probes. The Ir(III) complex 9, [Ir(phq)2(phen)]PF6 (where phq 1⁄4 2-phenylquinoline; phen 1⁄4 1,10-phenanthroline), exhibited high luminescence in the presence of G-quadruplex DNA compared to dsDNA and ssDNA, and was employed to construct a label-free G-quadrup...

Telomeric repeat-containing RNA (TERRA) is important for telomere regulation, but the structural basis for how TERRA localizes to chromosome ends is unknown. Here we report on studies exploring whether the TERRA G-quadruplex structure is critical for binding to telomeres. We demonstrate that the telomeric protein TRF2 binds TERRA via interactions that necessitate the formation of a G-quadruplex...

Nucleic acid aptamers are generally obtained by in vitro selection. Some have G-rich consensus sequences with ability to fold into the four-stranded structures known as G-quadruplexes. A few G-quadruplex aptamers have proven to bind hemin to form a new class of DNAzyme with the peroxidase-like activity, which can be significantly promoted by appending an appropriate base-pairing duplex onto the...

The human BCL-2 gene contains a 39-bp GC-rich region upstream of the P1 promoter that has been shown to be critically involved in the regulation of BCL-2 gene expression. Inhibition of BCL-2 expression can decrease cellular proliferation and enhance the efficacy of chemotherapy. Here we report the major G-quadruplex formed in the Pu39 G-rich strand in this BCL-2 promoter region. The 1245G4 quad...

The use of time-resolved fluorescence measurements in studies of telomeric G-quadruplex folding and stability has been hampered by the complexity of fluorescence lifetime distributions in solution. The application of phasor diagrams to the analysis of time-resolved fluorescence measurements, collected from either frequency-domain or time-domain instrumentation, allows for rapid characterization...

Previous studies on the functional analysis of the human vascular endothelial growth factor (VEGF) promoter using the full-length VEGF promoter reporter revealed that the proximal 36-bp region (-85 to -50 relative to transcription initiation site) is essential for basal or inducible VEGF promoter activity in several human cancer cells. This region consists of a polypurine (guanine) tract that c...

Fluorescence anisotropy (FA) is a homogeneous, ratiometric, and real-time analytical technology. By selective labeling of a guanine (G)-quadruplex motif with tetramethylrhodamine (TMR), here, it is established that a large reduction in FA response can be specifically associated with the unfolding → folding transition of G-quadruplex structures. On the basis of fluorescence intensity, polarizati...

Zika virus has emerged as a global concern because neither a vaccine nor antiviral compounds targeting it exist. A structure for the positive-sense RNA genome has not been established, leading us to look for potential G-quadruplex sequences (PQS) in the genome. The analysis identified >60 PQSs in the Zika genome. To minimize the PQS population, conserved sequences in the Flaviviridae family wer...