Probing the Importance of the G-Quadruplex Grooves for the Activity of the Anti-HIV-Integrase Aptamer T30923

Abstract

In this paper, we report studies concerning four variants of the G-quadruplex forming anti-HIV-integrase aptamer T30923, in which specific 2′-deoxyguanosines have been singly replaced by 8-methyl-2′-deoxyguanosine residues, with the aim to exploit the methyl group positioned in the G-quadruplex grooves as a steric probe to investigate the interaction aptamer/target. Although, the various modified aptamers differ in the localization of the methyl group, NMR, circular dichroism (CD), electrophoretic and molecular modeling data suggest that all of them preserve the ability to fold in a stable dimeric parallel G-quadruplex complex resembling that of their natural counterpart T30923. However, the biological data have shown that the T30923 variants are characterized by different efficiencies in inhibiting the HIV-integrase, thus suggesting the involvement of the G-quadruplex grooves in the aptamer/target interaction.

Lack of efficacy of mono‐mode of action therapeutics in COVID‐19 therapy ‐ How the lack of predictive power of preclinical cell and animal studies leads developments astray

“…Aptamers, already the focus of interest for antiviral treatment, including for SARS‐CoV (Esposito et al, 2020 ; Jeon et al, 2004 ; Musafia et al, 2014 ; Song et al, 2020 ; Torabi et al, 2020 ), have at least in some cases the chance to be not only absolutely specific for one epitope but to also show (some) affinity with several oligonucleotide‐binding‐susceptible sequence sections for different proteins of the virus (Esposito et al, 2020 ; Tucker et al, 2012 ; Weisshoff et al, 2020 ). This way, a cumulative multi‐effect might result (multi‐mode of action), together increasing the chance of treatment success.…”