Biosensor-Surface Plasmon Resonance: Label-Free Method for Investigation of Small Molecule-Quadruplex Nucleic Acid Inter
Biosensor-surface plasmon resonance (SPR) technology is now well established as a quantitative approach for the study of nucleic acid interactions in real time, without the need for labeling any components of the interaction. The method provides real-time
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Introduction Noncanonical DNA structures, formed by conformational rearrangements of genome regions bearing specific base sequences, are a novel mechanism of gene regulation. Four-stranded G-rich helical structures, known as G-quadruplexes (G4), are among the most actively investigated noncanonical DNA arrangements [1–3]. Discovered in 1910 thanks to a curious phenomenon of guanosine gel formation [4], G-quadruplexes are now one of the main structural elements of the genome. Computational predictions using the pattern match d(G3+N1–7G3+N1–7G3+N1–7G3+), where N is any nucleotide base, have identified 375,000 putative quadruplex sequences in the human genome [5, 6]. These noncanonical DNA arrangements are usually found at the ends of human chro-
Danzhou Yang and Clement Lin (eds.), G-Quadruplex Nucleic Acids: Methods and Protocols, Methods in Molecular Biology, vol. 2035, https://doi.org/10.1007/978-1-4939-9666-7_4, © Springer Science+Business Media, LLC, part of Springer Nature 2019
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Ananya Paul et al.
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Fig. 1 Schematic outline of (a) a G-quadruplex tetrad and (b) folding topologies of DNA G-quadruplexes in presence of monovalent cations
mosomes (telomeric G-quadruplexes) [7, 8] as well as at promoter regions of many oncogenes, where there is a high population of guanine-rich sequences [9–12]. In physiological conditions, guanine bases can associate through a network of Hoogsteen bonds to form planar arrays known as G-tetrads (Fig. 1). The overlapping of G-tetrads then leads to the formation of more complex arrangements, G-quadruplex structures, which are stabilized by the presence of mono-cations (mainly Na+ or K+, Fig. 1) [13–15]. Interestingly, at telomeres, where there is an equilibrium between the single-stranded repeat of the TTAGGG sequence and its G-quadruplex-folded conformation, G-quadruplex structures are an attractive target for therapeutic intervention. In fact, as G-quadruplex-folded telomeres cannot be recognized by the telomerase enzyme, the stabilization of such arrangements by small molecules can lead to the indirect inhibition of the enzyme activity [16, 17]. This is an attractive approach for the development of new selective anticancer agents as the enzyme is expressed in 85–90% of tumor cells [18–20] while its activity is low, or even absent, in somatic cells [19]. Additionally, as previously mentioned, G-quadruplex structures have also been identified in transcriptional regulatory regions of genes and oncogenes, where they can play a role in
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expression control mechanisms [21, 22]. Transcriptional repression of oncogenes through small molecule-driven stabilization of these structures could also be seen as an emerging anticancer strategy
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