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Macrocyclic Receptors for Biomolecules and Biochemical Sensing
Published in Satish Kumar, Priya Ranjan Sahoo, Violet Rajeshwari Macwan, Jaspreet Kaur, Mukesh, Rachana Sahney, Macrocyclic Receptors for Environmental and Biosensing Applications, 2022
Satish Kumar, Priya Ranjan Sahoo, Violet Rajeshwari Macwan, Jaspreet Kaur, Mukesh, Rachana Sahney
Double-stranded nucleic acid strands can adopt a variety of conformations. Small DNA fragments can fold to form a hair-pin structure. The stabilized forms of hairpins are associated with the disease. G-quadruplex is another unique secondary structure of DNA which are formed by four guanine bases associated through Hoogsteen hydrogen bonding to form a square planar structure called a guanine tetrad (G-tetrad or G-quartet), two or more guanine tetrads (G-tracts, continuous runs of guanine) can stack on top of each other to form a G-quadruplex. These structures bind to a variety of proteins and form complexes, which play essential roles in G-quadruplex-mediated regulation processes. Many of these G-quadruplex binding proteins and/or their complexes with G-quadruplexes are potential drug targets.
Single-Molecule Biosensing by Fluorescence Resonance Energy Transfer
Published in Shuo Huang, Single-Molecule Tools for Bioanalysis, 2022
G-quadruplexes are secondary structures formed by tandem repeats of guanines [97], and play important roles in regulating telomere lengths in vivo [98–102]. Using smFRET, Lee et al. probed the dynamics of G-quadruplexes in human telomeric DNA [55]. Three conformations, one unfolded and two folded, were observed in a solution containing potassium ions. Each conformation could be further divided into two species, the long-lived and the short-lived (Figure 3.6b). The long-lived states, which result from the folded structures, are dominant in physiologically relevant conditions. Although rare under these conditions, the short-lived species determine the overall dynamics because they bridge the different long-lived species. The extremely diverse conformations of the human telomeric DNA may have mechanistic implications for the proteins and drugs that recognize G-rich sequences [103].
A hydroxyquinoline-appended ruthenium(II)-polypyridyl complex that induces and stabilizes G-quadruplex DNA
Published in Journal of Coordination Chemistry, 2019
Xuexue Xu, Shuang Wang, Yaxuan Mi, Huaqian Zhao, Zebao Zheng, Xiaolong Zhao
G-quadruplexes are functionally useful secondary DNA structures, comprising stacks of G-quartets that are stabilized through cyclic Hoogsteen hydrogen bonding [1, 2]. The G-quadruplex structures are abundant in human genome and are currently being regarded as appealing therapeutic targets [3–5]. Many G-rich regions such as proto-oncogenes of c-myc, c-kit and bcl-2 and telomeres have the ability to form G-quadruplexes [6–9]. It has been determined by crystallographic and NMR studies that human telomeric DNA consists of tandem repeats of sequence d[(TTAGGG)n] is rich in guanine residues and can fold into quadruplex structures [9]. The conversion of telomeric DNA to a G-quadruplex can inhibit the activity of telomerase, an enzyme inactive in most normal somatic cells, but overexpressed in above 85% of cancer cells and contributes to the immortality of these cells [10]. Thus, the design of small molecules that targets at the telomeric G-quadruplex is an active area in drug discovery.