2c2t: Difference between revisions
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|PDB= 2c2t |SIZE=350|CAPTION= <scene name='initialview01'>2c2t</scene>, resolution 1.50Å | |PDB= 2c2t |SIZE=350|CAPTION= <scene name='initialview01'>2c2t</scene>, resolution 1.50Å | ||
|SITE= <scene name='pdbsite=AC1:Gol+Binding+Site+For+Chain+B'>AC1</scene> | |SITE= <scene name='pdbsite=AC1:Gol+Binding+Site+For+Chain+B'>AC1</scene> | ||
|LIGAND= | |LIGAND= <scene name='pdbligand=39B:(S)-2,4-DIAMINO-5-((7,8-DICARBAUNDECABORAN-7-YL)METHYL)-6-METHYLPYRIMIDINE'>39B</scene>, <scene name='pdbligand=39E:(R)-2,4-DIAMINO-5-((7,8-DICARBAUNDECABORAN-7-YL)METHYL)-6-METHYLPYRIMIDINE'>39E</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=NDP:NADPH+DIHYDRO-NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NDP</scene> | ||
|ACTIVITY= [http://en.wikipedia.org/wiki/Dihydrofolate_reductase Dihydrofolate reductase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.5.1.3 1.5.1.3] | |ACTIVITY= <span class='plainlinks'>[http://en.wikipedia.org/wiki/Dihydrofolate_reductase Dihydrofolate reductase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.5.1.3 1.5.1.3] </span> | ||
|GENE= | |GENE= | ||
|DOMAIN= | |||
|RELATEDENTRY= | |||
|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2c2t FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2c2t OCA], [http://www.ebi.ac.uk/pdbsum/2c2t PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2c2t RCSB]</span> | |||
}} | }} | ||
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==Overview== | ==Overview== | ||
Two boron-containing, ortho-icosahedral carborane lipophilic antifolates were synthesized, and the crystal structures of their ternary complexes with human dihydrofolate reductase (DHFR) and dihydronicotinamide adenine dinucleotide phosphate were determined. The compounds were screened for activity against DHFR from six sources (human, rat liver, Pneumocystis carinii, Toxoplasma gondii, Mycobacterium avium, and Lactobacillus casei) and showed good to modest activity against these enzymes. The compounds were also tested for antibacterial activity against L. casei, M. tuberculosis H37Ra, and three M. avium strains and for cytotoxic activity against seven different human tumor cell lines. Antibacterial and cytotoxic activity was modest, with one sample, the closo-carborane 4, showing about 10-fold greater activity. The less toxic nido-carborane 2 was also tested as a candidate for boron neutron capture therapy, but showed poor tumor retention and low selectivity ratios for boron distribution in tumor tissue versus normal tissue. | Two boron-containing, ortho-icosahedral carborane lipophilic antifolates were synthesized, and the crystal structures of their ternary complexes with human dihydrofolate reductase (DHFR) and dihydronicotinamide adenine dinucleotide phosphate were determined. The compounds were screened for activity against DHFR from six sources (human, rat liver, Pneumocystis carinii, Toxoplasma gondii, Mycobacterium avium, and Lactobacillus casei) and showed good to modest activity against these enzymes. The compounds were also tested for antibacterial activity against L. casei, M. tuberculosis H37Ra, and three M. avium strains and for cytotoxic activity against seven different human tumor cell lines. Antibacterial and cytotoxic activity was modest, with one sample, the closo-carborane 4, showing about 10-fold greater activity. The less toxic nido-carborane 2 was also tested as a candidate for boron neutron capture therapy, but showed poor tumor retention and low selectivity ratios for boron distribution in tumor tissue versus normal tissue. | ||
==About this Structure== | ==About this Structure== | ||
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[[Category: Reynolds, R C.]] | [[Category: Reynolds, R C.]] | ||
[[Category: Riordan, J M.]] | [[Category: Riordan, J M.]] | ||
[[Category: lipophilic antifolate]] | [[Category: lipophilic antifolate]] | ||
[[Category: nadp]] | [[Category: nadp]] | ||
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[[Category: reductase]] | [[Category: reductase]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 02:15:28 2008'' | ||
