title: A single molecule study of a fluorescently labeled telomestatin derivative and G-quadruplex interactions.
abstract: The potential use of G-quadruplex (GQ) stabilizing small molecules as anti-cancer drugs has created a flurry of activity on various aspects of these molecules. Telomestatin and oxazole telomestatin derivatives (OTD) are some of the most prominent of such molecules, yet the underlying dynamics of their interactions with GQ and the extent of heterogeneities in these interactions are not known. We performed single molecule measurements to study binding kinetics, rotational freedom, and dwell time distributions of a Cy5-labeled OTD (L1Cy5-7OTD) as it interacted with several different GQ structures. Our measurements show that L1Cy5-7OTD dwells on more stable GQ for longer times and binds to such GQ with higher frequency. The dwell times showed a broad distribution, but were longer than a minute for a significant fraction of molecules (characteristic dwell time τ = 192 ± 15 s and τ = 98 ± 15 s for the more and less stable GQ, respectively). In addition, L1Cy5-7OTD might be able to bind to GQ in at least two different primary orientations and occasionally transition between these orientations. The dwell time in one of these orientations was significantly longer than that in the other one, suggesting different stabilities for different binding orientations.
authors.affiliation: Department of Physics, Kent State University, Kent, OH 44240, USA.
authors.forename: Parastoo
authors.initials: P
authors.lastname: Maleki
authors.affiliation: Department of Biotechnology and Life Science, Graduate School of Technology, Tokyo University of Agriculture and Technology, Koganei, Tokyo 184-8588, Japan.
authors.forename: Yue
authors.initials: Y
authors.lastname: Ma
authors.affiliation: Department of Biotechnology and Life Science, Graduate School of Technology, Tokyo University of Agriculture and Technology, Koganei, Tokyo 184-8588, Japan.
authors.forename: Keisuke
authors.initials: K
authors.lastname: Iida
authors.affiliation: Department of Biotechnology and Life Science, Graduate School of Technology, Tokyo University of Agriculture and Technology, Koganei, Tokyo 184-8588, Japan.
authors.forename: Kazuo
authors.initials: K
authors.lastname: Nagasawa
authors.affiliation: Department of Physics, Kent State University, Kent, OH 44240, USA hbalci@kent.edu.
authors.forename: Hamza
authors.initials: H
authors.lastname: Balci
mesh_terms: D001665:Binding Sites; D002232:Carbocyanines / Q000737:chemistry; D031541:Fluorescence Resonance Energy Transfer; D005456:Fluorescent Dyes / Q000737:chemistry; D054856:G-Quadruplexes; D006801:Humans; D010080:Oxazoles / Q000737:chemistry* / Q000378:metabolism; D010957:Plasmids / Q000737:chemistry* / Q000378:metabolism; D000072760:Single Molecule Imaging; D013194:Staining and Labeling / Q000379:methods
chemical_list: D002232:Carbocyanines; D005456:Fluorescent Dyes; D010080:Oxazoles; C085321:cyanine dye 5; C431888:telomestatin