A Third Mode of DNA Binding: Phosphate Clamps by a Polynuclear Platinum Complex
详细信息 查看全文
- 作者：Seiji Komeda ; Tinoush Moulaei ; Kristen Kruger Woods ; Masahiko Chikuma ; Nicholas P. Farrell ; Loren Dean Williams
- 刊名：Journal of the American Chemical Society
- 出版年：2006
- 出版时间：December 20, 2006
- 年：2006
- 卷：128
- 期：50
- 页码：16092 - 16103
- 全文大小：1067K
- 年卷期：v.128,no.50(December 20, 2006)
- ISSN：1520-5126
文摘
We describe a 1.2 Å X-ray structure of a double-stranded B-DNA dodecamer (the DickersonDodecamer, DDD, [d(CGCGAATTCGCG)]2) associated with a cytotoxic platinum(II) complex, [{trans-Pt(NH3)2(NH2(CH2)6(NH3+)}2-
-{trans-Pt(NH3)2(NH2(CH2)6NH2)2}] (TriplatinNC). TriplatinNC is a multifunctionalDNA ligand, with three cationic Pt(II) centers, and directional hydrogen bonding functionalities, linked byflexible hydrophobic segments, but without the potential for covalent interaction. TriplatinNC does notintercalate nor does it bind in either groove. Instead, it binds to phosphate oxygen atoms and thus associateswith the backbone. The three square-planar tetra-am(m)ine Pt(II) coordination units form bidentate N···O···Ncomplexes with OP atoms, in a motif we call the Phosphate Clamp. The geometry is conserved among the8 observed phosphate clamps in this structure. The interaction appears to prefer O2P over O1P atoms(frequency of interaction is O2P > O1P, base and sugar oxygens > N). The high repetition and geometricregularity of the motif suggests that this type of Pt(II) center can be developed as a modular nucleic acidbinding device with general utility. TriplatinNC extends along the phosphate backbone, in a mode of bindingwe call "Backbone Tracking" and spans the minor groove in a mode of binding we call "Groove Spanning".Electrostatic forces appear to induce modest DNA bending into the major groove. This bending may berelated to the direct coordination of a sodium cation by a DNA base, with unprecedented inner-shell (direct)coordination of penta-hydrated sodium at the O6 atom of a guanine.
-{trans-Pt(NH3)2(NH2(CH2)6NH2)2}] (TriplatinNC). TriplatinNC is a multifunctionalDNA ligand, with three cationic Pt(II) centers, and directional hydrogen bonding functionalities, linked byflexible hydrophobic segments, but without the potential for covalent interaction. TriplatinNC does notintercalate nor does it bind in either groove. Instead, it binds to phosphate oxygen atoms and thus associateswith the backbone. The three square-planar tetra-am(m)ine Pt(II) coordination units form bidentate N···O···Ncomplexes with OP atoms, in a motif we call the Phosphate Clamp. The geometry is conserved among the8 observed phosphate clamps in this structure. The interaction appears to prefer O2P over O1P atoms(frequency of interaction is O2P > O1P, base and sugar oxygens > N). The high repetition and geometricregularity of the motif suggests that this type of Pt(II) center can be developed as a modular nucleic acidbinding device with general utility. TriplatinNC extends along the phosphate backbone, in a mode of bindingwe call "Backbone Tracking" and spans the minor groove in a mode of binding we call "Groove Spanning".Electrostatic forces appear to induce modest DNA bending into the major groove. This bending may berelated to the direct coordination of a sodium cation by a DNA base, with unprecedented inner-shell (direct)coordination of penta-hydrated sodium at the O6 atom of a guanine.