title: Positional impact of fluorescently modified G-tetrads within polymorphic human telomeric G-quadruplex structures.
abstract: Emissive C8-aryl-2'-deoxyguanosines placed within G-tetrads of G-quadruplex structures are useful probes for distinguishing G-quadruplexes from duplex structures using fluorescence spectroscopy. Here, we report the positional impact of C8-furyl-dG ((Fur)dG) on G-quadruplex folding in the human telomere 22-mer oligonucleotide (HTelo22, (d[AG3(T2AG3)3])). The (Fur)dG probe was inserted into four different positions within the three unique G-tetrads of HTelo22, and G-quadruplex folding was monitored by UV-vis thermal denaturation, circular dichroism, and fluorescence spectroscopy. Our studies demonstrate the impacts of C8-aryl-dG adduct formation on G-quadruplex polymorphism in K(+) solution and in the presence of the additives and cosolutes, CH3CN, polyethylene glycol (PEG-600), and N-methyl mesoporphyrin IX (NMM). Our experiments predict that C8-aryl-dG derivatives can serve as useful tools for various in vitro studies aimed at understanding both the implications of DNA adduct formation within G-quadruplex structures and the unique implications imposed by various folding topologies on biological function/recognition.
authors.affiliation: Departments of Chemistry and Toxicology, University of Guelph, Guelph, Ontario, Canada N1G 2W1.
authors.forename: Michael
authors.initials: M
authors.lastname: Sproviero
authors.affiliation: Departments of Chemistry and Toxicology, University of Guelph, Guelph, Ontario, Canada N1G 2W1.
authors.forename: Kaila L
authors.initials: KL
authors.lastname: Fadock
authors.affiliation: Departments of Chemistry and Toxicology, University of Guelph, Guelph, Ontario, Canada N1G 2W1.
authors.forename: Aaron A
authors.initials: AA
authors.lastname: Witham
authors.affiliation: Departments of Chemistry and Toxicology, University of Guelph, Guelph, Ontario, Canada N1G 2W1.
authors.forename: Richard A
authors.initials: RA
authors.lastname: Manderville
mesh_terms: D002942:Circular Dichroism; D005456:Fluorescent Dyes / Q000737:chemistry*; D054856:G-Quadruplexes; D006801:Humans; D016615:Telomere
chemical_list: D005456:Fluorescent Dyes