2p95: Difference between revisions
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New page: left|200px<br /> <applet load="2p95" size="450" color="white" frame="true" align="right" spinBox="true" caption="2p95, resolution 2.20Å" /> '''Factor xa in comple... |
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[[Image:2p95. | [[Image:2p95.jpg|left|200px]]<br /><applet load="2p95" size="350" color="white" frame="true" align="right" spinBox="true" | ||
<applet load="2p95" size=" | |||
caption="2p95, resolution 2.20Å" /> | caption="2p95, resolution 2.20Å" /> | ||
'''Factor xa in complex with the inhibitor 5-chloro-N-((1R,2S)-2-(4-(2-oxopyridin-1(2H)-YL)benzamido) cyclopentyl)thiophene-2-carboxamide'''<br /> | '''Factor xa in complex with the inhibitor 5-chloro-N-((1R,2S)-2-(4-(2-oxopyridin-1(2H)-YL)benzamido) cyclopentyl)thiophene-2-carboxamide'''<br /> | ||
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==Overview== | ==Overview== | ||
In the search of Factor Xa (FXa) inhibitors structurally different from, the pyrazole-based series, we identified a viable series of enantiopure, cis-(1R,2S)-cycloalkyldiamine derivatives as potent and selective, inhibitors of FXa. Among them, cyclohexyldiamide 7 and cyclopentyldiamide, 9 were the most potent neutral compounds, and had good anticoagulant, activity comparable to the pyrazole-based analogs. Crystal structures of, 7-FXa and 9-FXa illustrate binding similarities and differences between, the five- and the six-membered core systems, and provide rationales for, the observed SAR of P1 and linker moieties. | In the search of Factor Xa (FXa) inhibitors structurally different from, the pyrazole-based series, we identified a viable series of enantiopure, cis-(1R,2S)-cycloalkyldiamine derivatives as potent and selective, inhibitors of FXa. Among them, cyclohexyldiamide 7 and cyclopentyldiamide, 9 were the most potent neutral compounds, and had good anticoagulant, activity comparable to the pyrazole-based analogs. Crystal structures of, 7-FXa and 9-FXa illustrate binding similarities and differences between, the five- and the six-membered core systems, and provide rationales for, the observed SAR of P1 and linker moieties. | ||
==About this Structure== | ==About this Structure== | ||
2P95 is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with ME5 as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/Coagulation_factor_Xa Coagulation factor Xa], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.21.6 3.4.21.6] Full crystallographic information is available from [http:// | 2P95 is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=ME5:'>ME5</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/Coagulation_factor_Xa Coagulation factor Xa], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.21.6 3.4.21.6] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2P95 OCA]. | ||
==Reference== | ==Reference== | ||
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[[Category: serine protease]] | [[Category: serine protease]] | ||
''Page seeded by [http:// | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Jan 23 14:26:16 2008'' | ||
