Sandbox Reserved 430: Difference between revisions
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There are three fundamental components in the mechanism of cisplatin – cisplatin, DNA, and HMG-protein. Cisplatin makes contact with the cell membrane and enters the cell through active transport, but some molecules are passively diffused. This platinum-based drug acts in vivo by <scene name='Sandbox_Reserved_430/Guanine_in_black_caption/2'>binding</scene> to two consecutive adjacent '''guanine''' bases in DNA leading to the loss of its chlorine atoms for the nitrogen on the guanine; this occurs to better balance the platinum charge.<ref> David, G.S. The Molecular Perspective: Cisplatin. doi: 10.1634/theoncologist.11-3-316 The Oncologist March 2006 vol. 11 no. 3 316-317.</ref> The binding of cisplatin creates a 49<scene name='Sandbox_Reserved_430/49_bend_caption/1'>49°</scene> bend with an overall helix bend of 78<scene name='Sandbox_Reserved_430/78_bend/1'>78°</scene>, which is crucial to cisplatin’s role as an anticancer drug.[5] The bend in the <scene name='Sandbox_Reserved_430/Hmg-proetin_bound/1'>DNA</scene>, as seen in pdb 1ckt, allows for <font color='magenta'>HMG-protein</font> to bind to the DNA, and when bound it inserts a wedge like phenol group of '''phenylalanine''' <scene name='Sandbox_Reserved_430/37_phenylalanine/2'>37</scene> into the wind minor grove. HMG-proteins, high mobility group-proteins, are found everywhere and regulate transcription, replication, recombination and repair, and once bound to the DNA it de-stacks the <font color='cyan'>nucleotide base pairs </font>, which in turn kinks the already mutated DNA. With the HMG-protein bound to the DNA, the cell cannot properly repair the DNA, leading to apoptosis.<ref> Gelasco, Andrew. "NMR solution and structure of DNA Dodecamer Duplex Containing cis-Diammaineplatium" Department of Chemistry, MIT:1998</ref> | There are three fundamental components in the mechanism of cisplatin – cisplatin, DNA, and HMG-protein. Cisplatin makes contact with the cell membrane and enters the cell through active transport, but some molecules are passively diffused. This platinum-based drug acts in vivo by <scene name='Sandbox_Reserved_430/Guanine_in_black_caption/2'>binding</scene> to two consecutive adjacent '''guanine''' bases in DNA leading to the loss of its chlorine atoms for the nitrogen on the guanine; this occurs to better balance the platinum charge.<ref> David, G.S. The Molecular Perspective: Cisplatin. doi: 10.1634/theoncologist.11-3-316 The Oncologist March 2006 vol. 11 no. 3 316-317.</ref> The binding of cisplatin creates a 49<scene name='Sandbox_Reserved_430/49_bend_caption/1'>49°</scene> bend with an overall helix bend of 78<scene name='Sandbox_Reserved_430/78_bend/1'>78°</scene>, which is crucial to cisplatin’s role as an anticancer drug.[5] The bend in the <scene name='Sandbox_Reserved_430/Hmg-proetin_bound/1'>DNA</scene>, as seen in pdb 1ckt, allows for <font color='magenta'>HMG-protein</font> to bind to the DNA, and when bound it inserts a wedge like phenol group of '''phenylalanine''' <scene name='Sandbox_Reserved_430/37_phenylalanine/2'>37</scene> into the wind minor grove. HMG-proteins, high mobility group-proteins, are found everywhere and regulate transcription, replication, recombination and repair, and once bound to the DNA it de-stacks the <font color='cyan'>nucleotide base pairs </font>, which in turn kinks the already mutated DNA. With the HMG-protein bound to the DNA, the cell cannot properly repair the DNA, leading to apoptosis.<ref> Gelasco, Andrew. "NMR solution and structure of DNA Dodecamer Duplex Containing cis-Diammaineplatium" Department of Chemistry, MIT:1998</ref> | ||
This link shows a video on the mechanism of cisplatin.[http://www.youtube.com/watch?v=Wq_up2uQRDo] | This link shows a video on the mechanism of cisplatin.[http://www.youtube.com/watch?v=Wq_up2uQRDo] | ||
