Sandbox Reserved 430: Difference between revisions

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The figure to the right shows <scene name='Sandbox_Reserved_430/Cisplatin_intro_with_caption/2'>cisplatin</scene> bound to a 12 base pair double stranded DNA. Cisplatin, cis-PtCl2(NH3)2, is an “alkylating-like” chemotherapy drug, administered intravenously, used in the treatment of various types of cancer.

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~~/1'>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. The binding of cisplatin creates a 49<scene name='Sandbox_Reserved_430/49_bend/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 HMG-protein 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 nucleotide base pairs , which in turn kinks the already mutated DNA.[2] With the HMG-protein bound to the DNA, the cell cannot properly repair the DNA, leading to apoptosis.

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/1'>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. The binding of cisplatin creates a 49<scene name='Sandbox_Reserved_430/49_bend/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 HMG-protein 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 nucleotide base pairs , which in turn kinks the already mutated DNA.[2] With the HMG-protein bound to the DNA, the cell cannot properly repair the DNA, leading to apoptosis.

Unfortunately, there is not yet a definitive way to regulate which cells are affected by cisplatin, so the cytotoxic effects damage normal cells as well, in particular rapidly dividing cells such as those found in the gastrointestinal tract, bone marrow, testicles, ovaries, and hair growth. It is the foundation to many combination treatments for cancers, but not all cancers are effected by cisplatin, the majority of patients using cisplatin will relapse with platinum resistant diseases. Another way cisplatin can be in effective, is when the cancers gets too old; when a tumor starts out it divides more frequently and this is when it is effected. This same logic goes for solid tumors, other treatments are needed for these types of issues.

Sandbox Reserved 430: Difference between revisions

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 The figure to the right shows <scene name='Sandbox_Reserved_430/Cisplatin_intro_with_caption/2'>cisplatin</scene> bound to a 12 base pair double stranded DNA.  Cisplatin, cis-PtCl2(NH3)2, is an “alkylating-like” chemotherapy drug, administered intravenously, used in the treatment of various types of cancer.
-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/1'>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.  The binding of cisplatin creates a 49<scene name='Sandbox_Reserved_430/49_bend/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.[2]  With the HMG-protein bound to the DNA, the cell cannot properly repair the DNA, leading to apoptosis.
+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/1'>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.  The binding of cisplatin creates a 49<scene name='Sandbox_Reserved_430/49_bend/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.[2]  With the HMG-protein bound to the DNA, the cell cannot properly repair the DNA, leading to apoptosis.
 Unfortunately, there is not yet a definitive way to regulate which cells are affected by cisplatin, so the cytotoxic effects damage normal cells as well, in particular rapidly dividing cells such as those found in the gastrointestinal tract, bone marrow, testicles, ovaries, and hair growth.  It is the foundation to many combination treatments for cancers, but not all cancers are effected by cisplatin, the majority of patients using cisplatin will relapse with platinum resistant diseases.  Another way cisplatin can be in effective, is when the cancers gets too old; when a tumor starts out it divides more frequently and this is when it is effected.  This same logic goes for solid tumors, other treatments are needed for these types of issues.