Crystal and molecular structure of cis-[Pt(NH3)2(Guo)2]Cl3/2(ClO4)1/2.7H2O and anticancer activity of cis-[Pt(NH3)2(Puo)2]Cl2 complexes

Cramer, Roger E.; Dahlstrom, Phillip L.; Seu, Michael J. T.; Norton, Ted R.; Kashiwagi, Midori

doi:10.1021/ic50203a031

Cited by 82 publications

(57 citation statements)

References 3 publications

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“…suggests that Cu2+ ions bind to the N7 position of the guanine bases, in the major groove of DNA. This type of complexation appears to be similar to that taking place with cis-DDP (16), which is known from crystallographic studies to bind at the N7 site of guanine (20). However, binding of Cu(WI) to the Ni position of guanine bases cannot be discarded, and the present results are also be compatible with interstrand bridging through simultaneous binding to the N3 position of cytidine.…”

Section: Resultssupporting

confidence: 78%

A laser Raman spectroscopic study of the interaction of calf-thymus DNA with Cu(II) and Pb(II) ions: metal ion binding and DNA conformational changes

1988

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The interaction of calf-thymus DNA with Cu(II) and Pb(II) ions has been investigated in H2O and D2O solutions at physiological pH, using laser Raman spectroscopy. The results confirm the destabilizing effect of Cu2+ ions, which are shown to bind strongly to the guanine and cytidine bases, perturbing the A-T base pairs and disrupting the double-helical structure of DNA, whose conformation is markedly altered by these interactions. Earlier claims that Pb2+ ions destabilize DNA are not supported by the present study. These ions are found to interact only weakly with the nucleic bases, binding to the N7 position of the guanine bases and also interacting with the A-T pairs. Both types of ions are found to interact with the charged phosphate groups of DNA, although these sites are preferred over the nucleic bases by Pb2+ ions.

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Section: Resultssupporting

confidence: 78%

A laser Raman spectroscopic study of the interaction of calf-thymus DNA with Cu(II) and Pb(II) ions: metal ion binding and DNA conformational changes

1988

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“…The geometries of the bases were frozen and one-dimensional energy curves were calculated. It was found that the Pt-N and Pt-0 equilibrium distances for the various ligands are close to 2.0 A in all cases which is in agreement with experimental observations (31).…”

Section: Ligand Bindingsupporting

confidence: 90%

“…A novel cis-Pt(NH 3 ) 2 +l intrastrand complex with a dC(syn)pdG(antl) segment of DNA.Crystal structures of cis-Pt(NH 3 h+ 2 with RNA (33) and B-ONA(7,31,34,35) show that the PDA ligates to N7(G) with bond lengths of 1.8 A-2.31 A. With stacked base pairs ligation to 06(G) with a distance (7 ,33) of 3.34 A (34) occurs rather than intrastrand dGpdC binding.…”

mentioning

confidence: 99%

A Theoretical Model for the Binding of Cis-Pt(NH₃)₂⁺²to DNA

Miller

Taylor

Basch

et al. 1985

Journal of Biomolecular Structure and Dynamics

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The binding of cis-Pt(NH3)2B1B2 to the bases B1 and B2, i.e., guanine (G), cytosine (C), adenine (A), and thymine (T), of DNA is studied theoretically. The components of the binding are analyzed and a model structure is proposed for the intrastrand binding to the dB1pdB2 sequence of a kinked double helical DNA. Quantum mechanical calculations of the ligand binding energy indicates that cis-Pt(NH3)2(+2) (cis-PDA) binds to N7(G), N3(C), O2(C), O6(G), N3(A), N7(A), O4(T) and O2(T) in order of decreasing binding energy. Conformational analysis provides structures of kinked DNA in which adjacent bases chelate to cis-PDA. Only bending toward the major groove allows the construction of acceptable square planar complexes. Examples are presented for kinks of -70 degrees and -40 degrees at the receptor site to orient the base pairs for ligand binding to B1 and B2 to form a nearly square planar complex. The energies for complex formation of cis-PDA to the various intra-strand base sites in double stranded DNA are estimated. At least 32 kcal/mole separates the energetically favorable dGpdG.cis-PDA chelate from the dCpdG.cis-PDA chelate. All other possible chelate structures are much higher in energy which correlates with their lack of observation in competition with the preferred dGpdG chelate. The second most favorable ligand energy occurs with N3(C). A novel binding site involving dC(N3)pdG(N7) is examined. Denaturation can result in an anti----syn rotation of C about its glycosidic bond to place N3(C) in the major groove for intrastrand binding in duplex DNA. This novel intrastrand dCpdG complex and the most favored dGpdG structure are illustrated with stereographic projections.

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“…33,46−49 With a nonbulky L, rotation about the Pt−N7 bond is fast on the NMR time scale, and the single H8 NMR signal observed typically for each unique G represents the time average of the two guanine orientations. 43,[45][46][47][48]50,51 DNA adducts of the monofunctional complex, [Pt(dien)-Cl]Cl (dien = diethylenetriamine), have been studied extensively as a "control" useful in understanding the nature of DNA binding of difunctional Pt(II) anticancer drugs. 51−56 From the data on Pt(dien)(G) adducts, 51 it is clear that dien is a rather small nonbulky carrier ligand.…”

Section: ■ Introductionmentioning

confidence: 99%

Guanine Nucleobase Adducts Formed by [Pt(di-(2-picolyl)amine)Cl]Cl: Evidence That a Tridentate Ligand with Only in-Plane Bulk Can Slow Guanine Base Rotation

2012

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Pt(II) complexes bind preferentially at N7 of G residues of DNA, causing DNA structural distortions associated with anticancer activity. Some distortions induced by difunctional cisplatin are also found for monofunctional Pt(II) complexes with carrier ligands having bulk projecting toward the guanine base. This ligand bulk can be correlated with impeded rotation about the Pt-N7(guanine) bond. Pt(N(H)dpa)(G) adducts (N(H)dpa = di-(2-picolyl)amine, G = 5'-GMP, 5'-GDP, 5'-GTP, guanosine, 9-EtG, and 5'-IMP) were used to assess whether a tridentate carrier ligand having bulk concentrated in the coordination plane can impede guanine nucleobase rotation. Because the Pt(N(H)dpa) moiety contains a mirror plane but is unsymmetrical with respect to the coordination plane, Pt(N(H)dpa)(G) adducts can form anti or syn rotamers with the guanine O6 and the central N-H of N(H)dpa on the opposite or the same side of the coordination plane, respectively. The observation of two sharp, comparably intense guanine H8 NMR signals provided evidence that these Pt(N(H)dpa)(G) adducts exist as mixtures of syn and anti rotamers, that rotational interchange is impeded by N(H)dpa, and that the key interactions involves steric repulsions between the pyridyl and guanine rings. The relative proximity of the guanine H8 to the anisotropic pyridyl rings allowed us to conclude that the syn rotamer was usually more abundant. However, the anti rotamer was more abundant for the Pt(N(H)dpa)(5'-GTP) adduct, in which a hydrogen bond between the 5'-GTP γ-phosphate group and the N(H)dpa central N-H is geometrically possible. In all previous examples of the influence of hydrogen bond formation on rotamer abundance in Pt(II) guanine adducts, these hydrogen bonding interactions occurred between ligand groups in cis positions. Thus, the role of a trans ligand group in influencing rotamer abundance, as found here, is unusual.

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Crystal and molecular structure of cis-[Pt(NH3)2(Guo)2]Cl3/2(ClO4)1/2.7H2O and anticancer activity of cis-[Pt(NH3)2(Puo)2]Cl2 complexes

Cited by 82 publications

References 3 publications

A laser Raman spectroscopic study of the interaction of calf-thymus DNA with Cu(II) and Pb(II) ions: metal ion binding and DNA conformational changes

A laser Raman spectroscopic study of the interaction of calf-thymus DNA with Cu(II) and Pb(II) ions: metal ion binding and DNA conformational changes

A Theoretical Model for the Binding of Cis-Pt(NH₃)₂⁺²to DNA

Guanine Nucleobase Adducts Formed by [Pt(di-(2-picolyl)amine)Cl]Cl: Evidence That a Tridentate Ligand with Only in-Plane Bulk Can Slow Guanine Base Rotation

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Crystal and molecular structure of cis-[Pt(NH3)2(Guo)2]Cl3/2(ClO4)1/2.7H2O and anticancer activity of cis-[Pt(NH3)2(Puo)2]Cl2 complexes

Cited by 82 publications

References 3 publications

A laser Raman spectroscopic study of the interaction of calf-thymus DNA with Cu(II) and Pb(II) ions: metal ion binding and DNA conformational changes

A laser Raman spectroscopic study of the interaction of calf-thymus DNA with Cu(II) and Pb(II) ions: metal ion binding and DNA conformational changes

A Theoretical Model for the Binding of Cis-Pt(NH3)2+2to DNA

Guanine Nucleobase Adducts Formed by [Pt(di-(2-picolyl)amine)Cl]Cl: Evidence That a Tridentate Ligand with Only in-Plane Bulk Can Slow Guanine Base Rotation

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A Theoretical Model for the Binding of Cis-Pt(NH₃)₂⁺²to DNA