2q1j: Difference between revisions
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==Overview== | ==Overview== | ||
Herein, we report on the identification of three potent glycine and | 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. | ||
==Disease== | |||
Known disease associated with this structure: Factor X deficiency OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=227600 227600]] | |||
==About this Structure== | ==About this Structure== | ||
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[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Protein complex]] | [[Category: Protein complex]] | ||
[[Category: Bigge, C | [[Category: Bigge, C F.]] | ||
[[Category: Cody, W | [[Category: Cody, W L.]] | ||
[[Category: Filipski, K | [[Category: Filipski, K J.]] | ||
[[Category: Finzel, B | [[Category: Finzel, B C.]] | ||
[[Category: Kohrt, J | [[Category: Kohrt, J T.]] | ||
[[Category: Zhang, E.]] | [[Category: Zhang, E.]] | ||
[[Category: CA]] | [[Category: CA]] | ||
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[[Category: zymogen]] | [[Category: zymogen]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 18:35:05 2008'' | ||
Revision as of 19:35, 21 February 2008
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The discovery of glycine and related amino acid-based factor xa inhibitors
OverviewOverview
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.
DiseaseDisease
Known disease associated with this structure: Factor X deficiency OMIM:[227600]
About this StructureAbout this Structure
2Q1J is a Protein complex structure of sequences from Homo sapiens with and as ligands. Active as Coagulation factor Xa, with EC number 3.4.21.6 Full crystallographic information is available from OCA.
ReferenceReference
The discovery of glycine and related amino acid-based factor Xa inhibitors., Kohrt JT, Filipski KJ, Cody WL, Bigge CF, La F, Welch K, Dahring T, Bryant JW, Leonard D, Bolton G, Narasimhan L, Zhang E, Peterson JT, Haarer S, Sahasrabudhe V, Janiczek N, Desiraju S, Hena M, Fiakpui C, Saraswat N, Sharma R, Sun S, Maiti SN, Leadley R, Edmunds JJ, Bioorg Med Chem. 2006 Jul 1;14(13):4379-92. Epub 2006 Mar 10. PMID:16529937
Page seeded by OCA on Thu Feb 21 18:35:05 2008
Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)
OCA- Pages with broken file links
- Coagulation factor Xa
- Homo sapiens
- Protein complex
- Bigge, C F.
- Cody, W L.
- Filipski, K J.
- Finzel, B C.
- Kohrt, J T.
- Zhang, E.
- CA
- FXI
- Blood coagulation
- Calcium
- Cleavage on pair of basic residues
- Coagulation fxa
- Egf-like domain
- Gamma-carboxyglutamic acid
- Glycoprotein
- Hydrolase
- Hydroxylation
- Polymorphism
- Protease
- Serine protease
- Zymogen