Abstract
G-quadruplexes constitute an important type of nucleic acid structure, which can be found in living cells and applied by cell machinery as pivotal regulatory elements. Importantly, robust development of SELEX technology and modern, nucleic acid-based therapeutic strategies targeted towards various molecules have also revealed a large group of potent aptamers whose structures are grounded in G-quadruplexes. In this review, we analyze further extension of tetraplexes by additional structural elements and investigate whether G-quadruplex junctions with duplex, hairpin, triplex, or second G-quadruplex motifs are favorable for aptamers stability and biological activity. Furthermore, we indicate the specific and pivotal role of the G-quadruplex domain and the additional structural elements in interactions with target molecules. Finally, we consider the potency of G-quadruplex junctions in future applications and indicate the emerging research area that is still waiting for development to obtain highly specific and effective nucleic acid-based molecular tools.
Highlights
Aptamers are single-stranded oligonucleotides with specified sequences which determine the adoption of a strictly defined spatial structure
A great supplement for the reports referring to aptamers with quadruplex–hairpin junctions is research concerning the structural analysis of model fragments representing genome sequences, which could provide some general information about the influence of a hairpin on the G-quadruplex structure
The biological activity of molecular tools based on G-quadruplexes can be successfully improved by adding additional structural elements
Summary
Aptamers are single-stranded oligonucleotides with specified sequences which determine the adoption of a strictly defined spatial structure This enables highly specific binding to target molecules and modulation of their activity [1]. Szostak, where systematic evolution of ligands by exponential enrichment (SELEX) has been discussed for the first time [2,3] This main method of aptamers development relies on the selection of oligonucleotides with the greatest affinity towards a target compound from the combinatorial library as a result of repeatable cycles of binding reactions and washing off unbound molecules [4]. The literature data collected in this review constitute a compendium of knowledge that might be potentially useful for the development of novel molecular tools or improvements of existing aptamers utility for therapeutic applications
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