2q1j: Difference between revisions
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New page: left|200px<br /> <applet load="2q1j" size="450" color="white" frame="true" align="right" spinBox="true" caption="2q1j, resolution 1.90Å" /> '''The discovery of gl... |
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[[Image:2q1j. | [[Image:2q1j.jpg|left|200px]]<br /><applet load="2q1j" size="350" color="white" frame="true" align="right" spinBox="true" | ||
<applet load="2q1j" size=" | |||
caption="2q1j, resolution 1.90Å" /> | caption="2q1j, resolution 1.90Å" /> | ||
'''The discovery of glycine and related amino acid-based factor xa inhibitors'''<br /> | '''The discovery of glycine and related amino acid-based factor xa inhibitors'''<br /> | ||
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==Overview== | ==Overview== | ||
Herein, we report on the identification of three potent glycine and, related amino acid-based series of FXa inhibitors containing a neutral P1, chlorophenyl pharmacophore. A X-ray crystal structure has shown that, constrained glycine derivatives with optimized N-substitution can greatly, increase hydrophobic interactions in the FXa active site. Also, the, substitution of a pyridone ring for a phenylsulfone ring in the P4, sidechain resulted in an inhibitor with enhanced oral bioavailability. | Herein, we report on the identification of three potent glycine and, related amino acid-based series of FXa inhibitors containing a neutral P1, chlorophenyl pharmacophore. A X-ray crystal structure has shown that, constrained glycine derivatives with optimized N-substitution can greatly, increase hydrophobic interactions in the FXa active site. Also, the, substitution of a pyridone ring for a phenylsulfone ring in the P4, sidechain resulted in an inhibitor with enhanced oral bioavailability. | ||
==About this Structure== | ==About this Structure== | ||
2Q1J 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 CA and FXI as [http://en.wikipedia.org/wiki/ligands ligands]. 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:// | 2Q1J 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=CA:'>CA</scene> and <scene name='pdbligand=FXI:'>FXI</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. 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=2Q1J OCA]. | ||
==Reference== | ==Reference== | ||
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[[Category: zymogen]] | [[Category: zymogen]] | ||
''Page seeded by [http:// | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Jan 23 14:13:01 2008'' | ||
