Platination of the (T(2)G(4))(4) telomeric sequence: A structural and cross-linking study

The telomeric sequence (T(2)G(4))(4) was platinated in aqueous solutions co ntaining 50 mM LiClO4, NaClO4, or KClO4. The identification of the guanines which reacted with [Pt(NH3)(3)((HO)-O-2)](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 or der K+ > Na+ much greater than Li+. The tri-ammine complex yielded ca. 40-9 0% 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 structur e obtained by restrained molecular dynamics (rMD) simulations which confirm s the schematic model proposed by Williamson et al. [(1989) Cell 59, 871-88 0]. The bifunctional complexes cis- and trans-[Pt(NH3)(2)(H2O)(2)](2+) also first reacted with G9 and G15 and gave cross-linked adducts between two gu anines, which did not exceed 5% each of the products formed. Both the cis a nd trans isomers formed a G3-G15 platinum chelate, and the second also form ed bis-chelates at both ends of the G-quadruplex structure: G3-G15/G9-G21 a nd G3-G15/G9-G24. The rMD simulations showed that the cross-linking reactio ns by the trans complex can occur without disturbing the stacking of the th ree G-quartets.