Cation exchange in lipophilic G-quadruplexes: not all ion binding sites are equal.
Lipophilic guanosine derivatives that form G-quadruplexes are promising building blocks for ionophores and ion channels. Herein, cation exchange between solvated cations (K+ and NH4+) and bound cations in the G-quadruplex [G1]16.4Na+.4DNP- was studied by electrospray ionization mass spectrometry and solution 1H, 15N NMR spectroscopy. The ESI-MS and 1H NMR data provided evidence for the formation of mixed-cationic Na+, K+ G-quadruplexes. The use of 15NH4+ cations in NMR titrations, along with 15N-filtered 1H NMR and selective NOE experiments, identified two mixed-cationic intermediates in the cation exchange pathway from [G1]16.4Na+.4DNP- to [G1]16.4NH4+.4DNP-. The central Na+, bound between the two symmetry-related G8-Na+ octamers, exchanges with either K+ or NH4+ before the two outer Na+ ions situated within the C4 symmetric G8 octamers. A structural rationale, based on differences in the cations' octahedral coordination geometries, is proposed to explain the differences in site exchange for these lipophilic G-quadruplexes. Large cations such as Cs+ can be exchanged into the central cation binding site that holds the two symmetry-related C4 symmetric G8 octamer units together. The potential relevance of these findings to both supramolecular chemistry and DNA G-quadruplex structure are discussed.
Ma
Ling
L
Department of Chemistry and Biochemistry, University of Maryland, College Park, Maryland 20742, USA.
Iezzi
Maura
M
Kaucher
Mark S
MS
Lam
Yiu-Fai
YF
Davis
Jeffery T
JT
D001665:Binding Sites; D002414:Cations, Monovalent; D002586:Cesium / Q000737:chemistry / Q000378:metabolism; D004247:DNA / Q000737:chemistry* / Q000378:metabolism; D054856:G-Quadruplexes; D006151:Guanosine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism; D019906:Nuclear Magnetic Resonance, Biomolecular; D009690:Nucleic Acid Conformation; D011188:Potassium / Q000737:chemistry* / Q000378:metabolism; D000644:Quaternary Ammonium Compounds / Q000737:chemistry* / Q000378:metabolism; D012964:Sodium / Q000737:chemistry / Q000378:metabolism
D002414:Cations, Monovalent; D000644:Quaternary Ammonium Compounds; D006151:Guanosine; D002586:Cesium; D004247:DNA; D012964:Sodium; D011188:Potassium