title: A Simple Molecular Rotor for Defining Nucleoside Environment within a DNA Aptamer-Protein Complex.
abstract: The simple 5-furyl-2'-deoxyuridine ((Fur)dU) nucleobase exhibits dual probing characteristics displaying emissive sensitivity to changes in microenvironment polarity and to changes in solvent rigidity due to its molecular rotor character. Here, we demonstrate its ability to define the microenvironment of the various thymidine (T) loop residues within the thrombin binding aptamer (TBA) upon antiparallel G-quadruplex (GQ) folding and thrombin binding. The emissive sensitivity of the (Fur)dU probe to microenvironment polarity provides a diagnostic handle to distinguish T bases that are solvent-exposed within the GQ structure compared with probe location in the apolar duplex. Its molecular rotor properties then provide a turn-on fluorescent switch to identify which T residues within the GQ bind specifically to the protein target (thrombin). The fluorescence sensing characteristics of (Fur)dU make it an attractive tool for mapping aptamer-protein interactions at the nucleoside level for further development of modified aptamers for a wide range of diagnostic and therapeutic applications.
authors.affiliation: Departments of Chemistry and Toxicology, University of Guelph , Guelph, Ontario, Canada N1G 2W1.
authors.forename: Thomas Z
authors.initials: TZ
authors.lastname: Cservenyi
authors.affiliation: Departments of Chemistry and Toxicology, University of Guelph , Guelph, Ontario, Canada N1G 2W1.
authors.forename: Abigail J
authors.initials: AJ
authors.lastname: Van Riesen
authors.affiliation: Department of Health Science and Technology, ETH Zurich , Schmelzbergstrasse 9, 8092 Zurich, Switzerland.
authors.forename: Florence D
authors.initials: FD
authors.lastname: Berger
authors.affiliation: Departments of Chemistry and Toxicology, University of Guelph , Guelph, Ontario, Canada N1G 2W1.|Department of Chemistry, Faculty of Science, Suez Canal University , Ismailia, Egypt.
authors.forename: Ahmed
authors.initials: A
authors.lastname: Desoky
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: D052157:Aptamers, Nucleotide / Q000737:chemistry* / Q000378:metabolism; D002942:Circular Dichroism; D009705:Nucleosides / Q000737:chemistry* / Q000378:metabolism; D013050:Spectrometry, Fluorescence; D021241:Spectrometry, Mass, Electrospray Ionization; D013056:Spectrophotometry, Ultraviolet; D013917:Thrombin / Q000378:metabolism
chemical_list: D052157:Aptamers, Nucleotide; D009705:Nucleosides; D013917:Thrombin