d(GGGT)₄and r(GGGU)₄are both HIV-1 inhibitors and interleukin-6 receptor aptamers

Abstract

Aptamers are oligonucleotides that bind targets with high specificity and affinity. They have become important tools for biosensing, target detection, drug delivery and therapy. We selected the quadruplex-forming 16-mer DNA aptamer AID-1 [d(GGGT)4] with affinity for the interleukin-6 receptor (IL-6R) and identified single nucleotide variants that showed no significant loss of binding ability. The RNA counterpart of AID-1 [r(GGGU)4] also bound IL-6R as quadruplex structure. AID-1 is identical to the well-known HIV inhibitor T30923, which inhibits both HIV infection and HIV-1 integrase. We also demonstrated that IL-6R specific RNA aptamers not only bind HIV-1 integrase and inhibit its 3′ processing activity in vitro, but also are capable of preventing HIV de novo infection with the same efficacy as the established inhibitor T30175. All these aptamer target interactions are highly dependent on formation of quadruplex structure.

Modular Assembly of Cell-targeting Devices Based on an Uncommon G-quadruplex Aptamer

“…Even though CD-spectroscopy revealed formation of a G-quadruplex structure of mutant G24A ( Figure 2b ), concentration-dependent measurements clearly indicate that compared to C10.36 this mutant lacks Burkitt's lymphoma cell recognition properties ( Figure 2d ). Based on these results, we propose that C10.36 comprises a three-layer G-quadruplex structure arranged in a parallel orientation, as it has been described for other aptamers targeting the IL6R 21 , 22 and the telomere ends of chromosomal DNA. 23 According to this model, nucleotide T14 might be bulged out to avoid interference with G-quartet formation ( Figure 2a ).…”

Aptamers: Uptake mechanisms and intracellular applications

“…However, in some cases, very stable G-quadruplex aptamers have shown cross-binding to several different proteins. For example, the 16-mer G-quadruplex DNA aptamer binds HIV-integrase, interleukin-6, and HIV-gp120 [113,114]. The G-quadruplex RNA aptamers showed cross-binding to VEGF165, PDGF-AA, and PDGF-BB [115].…”

Interaction of hemin with quadruplex DNA

“…To do this, T30695 was selected as G-quadruplex DNA. T30695 is a G-quadruplex DNA aptamer that binds with high affinity to two different proteins, namely HIV 1 integrase (HIV-IN) and interleukin-6 receptor (IL-6R) [12][13][14].…”