Platination of the (T2G4)4 telomeric sequence: a structural and cross-linking study.
The telomeric sequence (T(2)G(4))(4) was platinated in aqueous solutions containing 50 mM LiClO(4), NaClO(4), or KClO(4). The identification of the guanines which reacted with [Pt(NH(3))(3)(H(2)O)](2+) revealed that the same type of folding exists in the presence of the three cations and that the latter determine the relative stabilities of the G-quadruplex structures in the order K(+) > Na(+) >> Li(+). The tri-ammine complex yielded ca. 40--90% of adducts, mono- and poly-platinated, bound to 4 guanines out of the 16 guanines in the sequence, in the decreasing amounts G9 > G15 >> G3 > G21. The formation of these adducts was interpreted with a G-quadruplex structure obtained by restrained molecular dynamics (rMD) simulations which confirms the schematic model proposed by Williamson et al. [(1989) Cell 59, 871--880]. The bifunctional complexes cis- and trans-[Pt(NH(3))(2)(H(2)O)(2)](2+) also first reacted with G9 and G15 and gave cross-linked adducts between two guanines, which did not exceed 5% each of the products formed. Both the cis and trans isomers formed a G3-G15 platinum chelate, and the second also formed bis-chelates at both ends of the G-quadruplex structure: G3-G15/G9-G21 and G3-G15/G9-G24. The rMD simulations showed that the cross-linking reactions by the trans complex can occur without disturbing the stacking of the three G-quartets.
Redon
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S
Laboratoire de Chimie et Biochimie Pharmacologiques et Toxicologiques, UMR 8601 CNRS, Université Paris V, 45 Rue des Saints-Pères, 75270 Paris Cedex 06, France.
Bombard
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Elizondo-Riojas
M A
MA
Chottard
J C
JC
D001483:Base Sequence; D002945:Cisplatin / Q000737:chemistry*; D003432:Cross-Linking Reagents / Q000737:chemistry*; D004247:DNA / Q000737:chemistry; D054856:G-Quadruplexes; D006147:Guanine / Q000737:chemistry; D018020:Lithium Compounds / Q000737:chemistry; D009690:Nucleic Acid Conformation; D009691:Nucleic Acid Denaturation; D009841:Oligonucleotides / Q000737:chemistry; D010472:Perchlorates / Q000737:chemistry; D017680:Potassium Compounds / Q000737:chemistry; D017670:Sodium Compounds / Q000737:chemistry; D016615:Telomere / Q000737:chemistry*; D013816:Thermodynamics
D003432:Cross-Linking Reagents; D018020:Lithium Compounds; D009841:Oligonucleotides; D010472:Perchlorates; D017680:Potassium Compounds; D017670:Sodium Compounds; C009006:potassium perchlorate; D006147:Guanine; D004247:DNA; C031068:sodium perchlorate; D002945:Cisplatin; C054684:lithium perchlorate