Sandbox Reserved 430: Difference between revisions

The original view shows a double stranded DNA helix and the cisplatin ligand. It is a "duplex dodecamer" d(CCTCTG*G*TCTCCGGAGACCAGAGG), and the asterisks are denoting which base pairs the Ciplatin binds to. This molecule is in its <scene name='Sandbox_Reserved_430/Z-dna_form_due_to_cisplatin/1'>A-DNA conformation due to Cisplatin</scene> which means it stll has the right handed helix, but the widened minor groove distorts its structure. To prove this, the animation shows the distance between intrastrand phosphate groups has been changed due to the insertion of the Cisplatin. Based on the chart found in <font color='purple'>([[Forms of DNA]])</font>, the distance should changed from 7 [Å] to 5.9 [Å]. It is much more rare than the common B-DNA[2]<scene name='Sandbox_Reserved_430/Intra-strand_phosphate/1'>Intra-strand Phosphate</scene> <ref>Takahara, P. M., Rosenzweig, A. C., Frederick, C. A., and Lippard, S. J. (1995) Nature 377, 649-652. Takahara, P. M., Frederick, C. A., and Lippard, S. J. (1996) J. Am. Chem. Soc 118, 12309-12321</ref>.  

<scene name='Sandbox_Reserved_430/Cisplatin_ligand/1'>Platination bond d(GpG)</scene>. The cisplatin ligand is a cis-diammineplatinum molecule, which is a platinum atom attached to two N7 nitrogen atoms, each apart of a <font color='blue'>guanine bases</font>, and two NH3 molecules attached to the other side. They attach to the 6 and 7 <font color='blue'>guanine bases</font> which links the two bases together and alters the bend in the helix by 49 degrees.The guanine still pair with the 18 and 19 <font color='red'>cytosine bases.</font><ref>Fichtinger-Schepman, A. M. J., van der Veer, J. L., den Hartog, J. H. J., Lohman, P. H. M., and Reedijk, J. (1985) Biochemistry

Normally, the Cisplatin molecule has two Cl atoms attached to Pt's last two electrons <font color='purple'>[PtCl2(NH3)2]</font>. The Cl atoms can be displaced by "aquation" to form <font color='purple'>[PtCl(H2O)(NH3)2]+</font>. The resulting ligand can be linked to bases now and guanine is the preferred choice. It can then cross-link as in the Cisplatin molecules shown above to form <font color='purple'>[Pt(guanine-DNA)2(NH3)2]+</font>.<ref>http://en.wikipedia.org/wiki/Cisplatin,last accessed 4/8/12.</ref> The N-Pt-N angles, two N7 nitrogens from the guanine base and two NH3 attached directly as part of the Cisplatin ligand, are planar and at 90 degrees, as well as each being a distance of 2.05 [Å] from the PT atom. Another interesting feature about the platinated lesion is in a 5 base section between C4-G21 and T8-A17. The minor groove of the molecule is roughly 9-12 [Å] with a depth range of roughly .4-2.5 [Å] which is much shorter than the B form with a depth of 6.5 [Å]<ref>Andrew Gelasco and Stephen J. Lippard* Department of Chemistry, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139