Dissertation Information for Debadeep BhattacharyyaNAME:
DEGREE:
DISCIPLINE:
SCHOOL: ADVISORS: COMMITTEE MEMBERS: MPACT Status: Fully Complete Title: Platinum complexes of heterocyclic ligands including DNA oligonucleotides Abstract: 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 A 2 ligands designed to slow dynamic interchange of conformers but allowing conformers to form, we found two of the other three conformers, ¥ÄHT1 = head-to-tail G* bases with a ¥Ä 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 PtA 2 system where A 2 = 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 \' -Me 2 bipy ). All of these retro ligands are planar, aromatic, and lack any ammine NH groups. Both 5,5 \' -Me 2 bipy 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 dcbipy Pt G 2 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 dcbipy Pt G 2 HH form suggest that the G bases assume an uncanted orientation. Both 5,5 \' -Me 2 bipy 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 ¥ÄHT conformers, a new fourth form, which became the most abundant form at pH ¡10.3, was observed for both 5,5 \' -Me 2 bipy Pt(d(G*pG*)) and 5,5 \' -dcbipy Pt(d(G*pG*)) adducts at pH ¡4. The ¥ÄHT conformer persisted but in low abundance at pH ¡10.3. This is the first evidence of a fourth form observed for cis -PtA 2 (d(G*pG*)) type adducts upon deprotonation. We present data on 5,5 \' -Me 2 bipy Pt and 5,5 \' -dcbipy Pt adducts with ss oligonucleotides (oligo) longer than d(GpG). In addition to the major HH1 form, a stable ¥ÄHT conformer was observed for all the oligo adducts regardless of flanking substituent. |
MPACT Scores for Debadeep BhattacharyyaA = 0 Advisors and Advisees Graph |