| In binding to DNA, the anticancer drug cisplatin forms preferentially a distorted G*G* adduct (G* = N7-platinated G). In the last decade, employing specially designed "retro" carrier A2 ligands designed to slow dynamic interchange of conformers but allowing conformers to form, we found two of the other three conformers, DeltaHT1 = head-to-tail G* bases with a Delta chirality and HH2 (2 denotes backbone propagation opposite to normal.) The studies presented here concentrate on unlinked complexes and single-stranded adducts formed with a novel type of PtA2 system where A2 = 2,2'-bipyridine-5,5' -dicarboxylate (5,5'-dcbipy), 2,2 '-bipyridine-4,4'-dicarboxylate ( 4,4'-dcbipy), and 5,5'-dimethyl-2,2 '-bipyridine (5,5'-Me2bipy ). All of these retro ligands are planar, aromatic, and lack any ammine NH groups. Both 5,5'-Me2bipy and 5,5'-dcbipy have H6 and H6' protons, which have singlet NMR signals and project toward the G* residues.; HT and HH rotamers were found for all the dcbipyPt G2 adducts by NMR spectroscopy. The relative distribution of conformers varied as a function of pH and identity of G. NMR and CD spectroscopic studies established the importance of phosphate group-cis G N1H interactions for stabilization of the dominant HT forms. The chemical shifts of the H8 signals of the dcbipyPtG 2 HH form suggest that the G bases assume an uncanted orientation.; Both 5,5'-Me2bipy and 5,5'-dcbipy allow coexistence of multiple conformers and also hinder dynamic motion in d(GpG) adducts. In addition to the HH1, HH2 and DeltaHT conformers, a new fourth form, which became the most abundant form at pH ∼10.3, was observed for both 5,5'-Me 2bipyPt(d(G*pG*)) and 5,5'-dcbipy Pt(d(G*pG*)) adducts at pH ∼4. The DeltaHT conformer persisted but in low abundance at pH ∼10.3. This is the first evidence of a fourth form observed for cis-PtA2(d(G*pG*)) type adducts upon NIH deprotonation.; We present data on 5,5'-Me2bipy Pt and 5,5'-dcbipyPt adducts with ss oligonucleotides (oligo) longer than d(GpG). In addition to the major HH1 form, a stable DeltaHT conformer was observed for all the oligo adducts regardless of flanking substituent. |
