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G-QUADRUPLEXES AS SENSING PROBES

DNA plays a fundamental role in all living organisms, as it is a crucial molecule responsible for the storage and copying of genetic information [1]. Previously, it has been assumed that DNA has a “passive” structure used only for the storage of genetic information. From the experiments carried out recently, it is evident that DNA is a very dynamic molecule, capable of forming a number of spatial arrangements. These structures include single-stranded hairpins, homoduplexes, triplexes, and quadruplexes [2]. Formerly these structures were considered an interesting phenomenon with a little practical meaning. Later it was found that the formation of these structures takes place under certain physiological conditions; therefore their involvement in recombination, regulation of gene expression and proliferation of tumour cells is assumed. Based on these facts it is not surprising that there is growing interest in the structures of nucleic acids as potential therapeutic drugs [3].

G-Quadruplexes
The most famous structures of DNA are highly ordered guanine quadruplexes (G-quadruplexes) composed of guanine quartets (G-quartets), which are formed from four guanine bases. In G-quartet each guanine is linked with neighbouring guanine via two hydrogen bonds by Hoogsteen pairing. These structures then stack on each other in a helical fashion, forming a G-quadruplex structure. G-quadruplexes are stabilized by hydrogen bonds and by the presence of alkali metal ions, which are located in the centre between two G-quartets. These ions are most frequently potassium or sodium cations, which are connected by electrostatic interactions on the guanine carbonyl [4-8].
G-quadruplexes are characterized by unique architecture and high stability [9]. Some sequences remain folded under physiological conditions and at temperatures above 90 °C [4]. G-quadruplexes are highly polymorphic and they can be classified in terms of the stoichiometric as unimolecular, bimolecular, and tetramolecular and also in terms of orientation as parallel, antiparallel or mixed. Structure of G-quadruplexes depends on the composition and length of the DNA, on the orientation of the chains and positions of the loops, and also on the nature of the cations [10]. Due to these modifications G-quadruplex structures can be created easily both intermolecularly and intramolecularly [1].
G-quadruplex structures have drawn the attention of researchers in medicinal chemistry, supramolecular chemistry, and nanotechnology [6, 11-13]. In addition, G-quadruplexes have been used as basic units in the formation of nanostructures [12]. Almost all G-quadruplex structures studied have been formed by one, two, or four G-rich strands [6]. G-quadruplex structures formed by three strands, leading to a tri-G-quadruplex species have been described recently by Zhou et al. [14]. This tri-G-quadruplex design may also provide a new avenue for creating nanoscale materials. Human telomeric DNA composed of (TTAGGG/CCCTAA)n repeats may form a classical Watson-Crick double helix. Each individual strand is also prone to quadruplex formation: the G-rich strand may adopt a G-quadruplex conformation involving G-quartets whereas the C-rich strand may fold into an i-motif based on intercalated C.C+ base pairs [15]. A number of research groups constructed different nanodevices based on switching between structures as induced by changes in environmental factors [16-18]. Zhou et al. [19] demonstrated the coexistence of a G-quadruplex and an i-motif in a single strand. This structure was built on the basis of the principle that G-quadruplex formation requires the presence of a G-quadruplex-compatible cation, whereas i-motif formation demands acidic conditions. The constructed nanodevice is very simple and can be rapidly converted into other structures by varying the stimulus, such as the pH value or cation.

G-quadruplexes form a complex with hemin (G-quadruplex/hemin) and are called DNAzymes. These complexes exhibit peroxidase-like activity and effectively catalyse the H2O2-mediated oxidation of 2,2'-azino-bis(3-ethylbenzothiazolin-6-sulfonic acid)diammonium salt (ABTS) [20-22]. Due to the ability to bind metal ions and other compounds, these DNAzymes can be used to detect Ag+, Cu2+, Pb2+, Hg2+, and Sr2+ ions [23-27]. This review is thus aimed at summarizing the facts about G-quadruplexes as sensing probes for determining of biologically active compounds.

Práce je spojená s projektem NanoBioTECell GA CR P102/11/1068

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