title: Observation of a Dynamic G-Tetrad Flip in Intramolecular G-Quadruplexes.
abstract: A MYC sequence forming an intramolecular G-quadruplex with a parallel topology was modified by the incorporation of 8-bromoguanosine (BrG) analogues in one of its outer G-tetrads. The propensity of theBrG analogues to adopt a syn glycosidic torsion angle results in an exceptional monomolecular quadruplex conformation featuring a complete flip of one tetrad while keeping a parallel orientation of all G-tracts as shown by circular dichroism and nuclear magnetic resonance spectroscopic studies. When substituting three of the four G-tetrad residues withBrG analogues, two coexisting quadruplex conformational isomers with an all-syn and all-anti outer G-quartet are approximately equally populated in solution. A dynamic interconversion of the two quadruplexes with an exchange rate (kex) of 0.2 s-1is demonstrated through the observation of exchange crosspeaks in rotating frame Overhauser effect spectroscopy and nuclear Overhauser effect spectroscopy experiments at 50 °C. The kinetic properties suggest disruption of the corresponding outer G-tetrad but not of the whole quadruplex core during the tetrad flip. Conformational syn-anti isomers with homopolar and heteropolar stacking interactions are nearly isoenergetic with a transition enthalpy of 18.2 kJ/mol in favor of the all-syn isomer.
authors.affiliation: Institute of Biochemistry, Ernst-Moritz-Arndt University Greifswald , Felix-Hausdorff-Strasse 4, D-17487 Greifswald, Germany.
authors.forename: Beatrice
authors.initials: B
authors.lastname: Karg
authors.affiliation: Institute of Biochemistry, Ernst-Moritz-Arndt University Greifswald , Felix-Hausdorff-Strasse 4, D-17487 Greifswald, Germany.
authors.forename: Linn
authors.initials: L
authors.lastname: Haase
authors.affiliation: Institute of Biochemistry, Ernst-Moritz-Arndt University Greifswald , Felix-Hausdorff-Strasse 4, D-17487 Greifswald, Germany.
authors.forename: Andrea
authors.initials: A
authors.lastname: Funke
authors.affiliation: Institute of Biochemistry, Ernst-Moritz-Arndt University Greifswald , Felix-Hausdorff-Strasse 4, D-17487 Greifswald, Germany.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Dickerhoff
authors.affiliation: Institute of Biochemistry, Ernst-Moritz-Arndt University Greifswald , Felix-Hausdorff-Strasse 4, D-17487 Greifswald, Germany.
authors.forename: Klaus
authors.initials: K
authors.lastname: Weisz
mesh_terms: D002152:Calorimetry, Differential Scanning; D002942:Circular Dichroism; D054856:G-Quadruplexes; D007536:Isomerism; D019906:Nuclear Magnetic Resonance, Biomolecular; D009690:Nucleic Acid Conformation