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  • Title: Stabilization and structure of telomeric and c-myc region intramolecular G-quadruplexes: the role of central cations and small planar ligands.
    Author: Gabelica V, Baker ES, Teulade-Fichou MP, De Pauw E, Bowers MT.
    Journal: J Am Chem Soc; 2007 Jan 31; 129(4):895-904. PubMed ID: 17243826.
    Abstract:
    A promising approach for anticancer strategies is the stabilization of telomeric DNA into a G-quadruplex structure. To explore the intrinsic stabilization of folded G-quadruplexes, we combined electrospray ionization mass spectrometry, ion mobility spectrometry, and molecular modeling studies to study different DNA sequences known to form quadruplexes. Two telomeric DNA sequences of different lengths and two DNA sequences derived from the NHE III1 region of the c-myc oncogene (Pu22 and Pu27) were studied. NH4+ and the ligands PIPER, TMPyP4, and the three quinacridines MMQ1, MMQ3, and BOQ1 were complexed with the DNA sequences to determine their effect on the stability of the G-quadruplexes. Our results demonstrate that G-quadruplex intramolecular folds are stabilized by NH4+ cations and the ligands listed. Furthermore, the ligands can be classified according to their ability to stabilize the quadruplexes and end stacking is shown to be the dominant mode for ligand attachment. In all cases our solvent-free experimental observations and theoretical modeling reveal structures that are highly relevant to the solution-phase structures.
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