G-quadruplexes constitute a unique class of nucleic acid structures formed by G-rich oligonucleotides of DNA- or RNA-type. Depending on their chemical nature, loops length, and localization in the sequence or structure molecularity, G-quadruplexes are highly polymorphic structures showing various folding topologies. They may be formed in the human genome where they are believed to play a pivotal role in the regulation of multiple biological processes such as replication, transcription, and translation. Thus, natural G-quadruplex structures became prospective targets for disease treatment. The fast development of systematic evolution of ligands by exponential enrichment (SELEX) technologies provided a number of G-rich aptamers revealing the potential of G-quadruplex structures as a promising molecular tool targeted toward various biologically important ligands. Because of their high stability, increased cellular uptake, ease of chemical modification, minor production costs, and convenient storage, G-rich aptamers became interesting therapeutic and diagnostic alternatives to antibodies. In this review, we describe the recent advances in the development of G-quadruplex based aptamers by focusing on the therapeutic and diagnostic potential of this exceptional class of nucleic acid structures.
G-quadruplexes (G4s) are non-canonical structures formed by guanine-rich sequences of DNA or RNA that have attracted increased attention as anticancer agents. This systematic study aimed to investigate the anticancer potential of five G4-forming, sequence-related DNA molecules in terms of their thermodynamic and structural properties, biostability and cellular uptake. The antiproliferative studies revealed that less thermodynamically stable G4s with three G-tetrads in the core and longer loops are more predisposed to effectively inhibit cancer cell growth. By contrast, highly structured G4s with an extended core containing four G-tetrads and longer loops are characterized by more efficient cellular uptake and improved biostability. Various analyses have indicated that the G4 structural elements are intrinsic to the biological activity of these molecules. Importantly, the structural requirements are different for efficient cancer cell line inhibition and favorable G4 cellular uptake. Thus, the ultimate antiproliferative potential of G4s is a net result of the specific balance among the structural features that are favorable for efficient uptake and those that increase the inhibitory activity of the studied molecules. Understanding the G4 structural features and their role in the biological activity of G-rich molecules might facilitate the development of novel, more potent G4-based therapeutics with unprecedented anticancer properties.
In comparison to other European countries, during the first months of the COVID-19 pandemic, Poland reported a relatively low number of confirmed cases of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections. To estimate the scale of the pandemic in Poland, a serosurvey of antibodies against SARS-CoV-2 was performed after the first wave of COVID-19 in Europe (March–May 2020). Within this study, we collected samples from 28 July to 24 September 2020 and, based on the ELISA results, we found that 1.67% (25/1500, 95% CI 1.13–2.45) of the Poznan (Poland) metropolitan area’s population had antibodies against SARS-CoV-2 after the first wave of COVID-19. However, the presence of anti-SARS-CoV-2 IgG antibodies was confirmed with immunoblotting in 56% (14/25) samples, which finally resulted in a decrease in seroprevalence, i.e., 0.93% (14/1500, 95% CI 0.56–1.56). The positive anti-SARS-CoV-2 IgG results were associated with age, occupation involving constant contact with people, travelling abroad, non-compliance with epidemiological recommendations and direct contact with the novel coronavirus. Our findings confirm the low SARS-CoV-2 incidence in Poland and imply that the population had little herd immunity heading into the second and third wave of the pandemic, and therefore, that herd immunity contributed little to preventing the high numbers of SARS-CoV-2 infections and COVID-19-related deaths in Poland during these subsequent waves.
A serosurvey of antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was performed between July and September 2020. Within this study, we found that 0.93% of the Poznan metropolitan area population had been exposed to SARS-CoV-2 after the first wave of coronavirus disease 2019 (COVID-19).
We systematically investigated the influence of locked nucleic acid (LNA), unlock nucleic acid (UNA), and 2’-O-methyl-RNA (2’-O-Me-RNA) residues on the thermal stability, structure folding topology, biological activity and enzymatic resistance of three sequence-related DNA G-quadruplexes. In order to better understand the mechanism of action of the studied modifications, a single-position substitution in the loops or G-tetrads was performed and their influence was analyzed for a total of twenty-seven modified G-quadruplex variants. The studies show that the influence of each modification on the physicochemical properties of G-quadruplexes is position-dependent, due to mutual interactions between G-tetrads, loops, and additional guanosine at 5’ or 3’ end. Nevertheless, the anticancer activity of the modified G-quadruplexes is determined by their structure, thus also by the local changes of chemical character of sugar moieties, what might influence the specific interactions with therapeutic targets. In general, UNA modifications are efficient modulators of the G-quadruplex thermodynamic stability, however they are poor tools to improve the anticancer properties. In contrast, LNA and 2’-O-Me-RNA modified G-quadruplexes demonstrated certain antiproliferative potential and might be used as molecular tools for designing novel G-quadruplex-based therapeutics.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.