L-Oligonucleotide aptamers (Spiegelmers) consist of non-natural L-configured nucleotides and are of particular therapeutic interest due to their high resistance to plasma nucleases. The anaphylatoxin C5a, a potent inflammatory mediator generated during complement activation that has been implicated with organ damage, can be efficiently targeted by Spiegelmers. Here, we present the first crystal...

Telomestatin (TMS: 1) is as a potent and selective telomeric G-quadruplex binder. Two molecules of TMS were suggested to be intercalated to one telomeric G-quadruplex according to docking study. In this paper, we designed and synthesized hexaoxazole TMS derivative (6OTD) dimer, and evaluated its G-quadruplex stabilizing ability.

A non-fluorescent naphthalene diimide (NDI) dimer, conjugating red and blue NDI dyes, becomes red/NIR emitting upon G-quadruplex binding. The fluorescence lifetime which is significantly different for the complexes, the G-quadruplex/dimer and the weakly emitting ds-DNA/dimer is the key feature for the development of new rationally engineered G-quadruplex sensors.

The interactions of a series of platinum(II) Schiff base complexes with c-myc G-quadruplex DNA were studied. Complex [PtL(1a)] (1 a; H(2)L(1a)=N,N'-bis(salicylidene)-4,5-methoxy-1,2-phenylenediamine) can moderately inhibit c-myc gene promoter activity in a cell-free system through stabilizing the G-quadruplex structure and can inhibit c-myc oncogene expression in cultured cells. The interaction...

Here we report the analysis of dual G-quadruplexes formed in the four repeats of the consensus sequence from the insulin-linked polymorphic region (ACAGGGGTGTGGGG; ILPR(n)(=4)). Mobilities of ILPR(n)(=4) in nondenaturing gel and circular dichroism (CD) studies confirmed the formation of two intramolecular G-quadruplexes in the sequence. Both CD and single molecule studies using optical tweezers...

The ribozyme-sensitive element NHE-III1 in the P1 promoter region of the important proto-oncogene c-myc contains many guanine (G)-rich sequences. Induction and stabilization of the G-quadruplex formed by NHE-III1 can downregulate c-myc expression. In the present study, we found that QPB-15e, a quinazoline derivative designed and synthesized by our laboratory, binds to and stabilizes the c-myc G...

The nuclease hypersensitivity element III(1) upstream of the P1 promoter of c-MYC controls 85-90% of the transcriptional activation of this gene. We have demonstrated that the purine-rich strand of the DNA in this region can form two different intramolecular G-quadruplex structures, only one of which seems to be biologically relevant. This biologically relevant structure is the kinetically favo...

G-quadruplexes have attracted growing attention as a potential cancer-associated target for both treatment and detection in recent years. For detection purpose, high specificity is one of the most important factors to be considered in G-quadruplex probe design. It is well known that end stacking and groove binding are two dominated quadruplex-ligand binding modes, and currently most reported G-...

The G-overhangs of telomeres are thought to adopt particular conformations, such as T-loops or G-quadruplexes. It has been suggested that G-quadruplex structures could be stabilized by specific ligands in a new approach to cancer treatment consisting in inhibition of telomerase, an enzyme involved in telomere maintenance and cell immortality. Although the formation of G-quadruplexes was demonst...

This review summarizes the results of structural studies carried out with analogs of G-quadruplexes built from natural nucleotides. Several dozens of base-, sugar-, and phosphate derivatives of the biological building blocks have been incorporated into more than 50 potentially quadruplex forming DNA and RNA oligonucleotides and the stability and folding topology of the resultant intramolecular,...