2f9v: Difference between revisions

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[[Image:2f9v.jpg|left|200px]]
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{{STRUCTURE_2f9v|  PDB=2f9v  |  SCENE=  }}  
{{STRUCTURE_2f9v|  PDB=2f9v  |  SCENE=  }}  


'''HCV NS3 protease domain with NS4a peptide and a ketoamide inhibitor with P1 and P2 cyclopropylalannines'''
===HCV NS3 protease domain with NS4a peptide and a ketoamide inhibitor with P1 and P2 cyclopropylalannines===




==Overview==
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Depeptidization efforts of the P(3)-P(2) region of P(3) capped alpha-ketoamide inhibitor of HCV NS3 serine protease 1 are reported. We clearly established that N-methylation of the P(2) nitrogen and modification of the P(2)' carboxylic acid terminus were essential for activity in the replicon assay.
The line below this paragraph, {{ABSTRACT_PUBMED_16387495}}, adds the Publication Abstract to the page
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{{ABSTRACT_PUBMED_16387495}}


==About this Structure==
==About this Structure==
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==Reference==
==Reference==
Depeptidization efforts on P3-P2' alpha-ketoamide inhibitors of HCV NS3-4A serine protease: effect on HCV replicon activity., Bogen SL, Ruan S, Liu R, Agrawal S, Pichardo J, Prongay A, Baroudy B, Saksena AK, Girijavallabhan V, Njoroge FG, Bioorg Med Chem Lett. 2006 Mar 15;16(6):1621-7. Epub 2006 Jan 4. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/16387495 16387495]
Depeptidization efforts on P3-P2' alpha-ketoamide inhibitors of HCV NS3-4A serine protease: effect on HCV replicon activity., Bogen SL, Ruan S, Liu R, Agrawal S, Pichardo J, Prongay A, Baroudy B, Saksena AK, Girijavallabhan V, Njoroge FG, Bioorg Med Chem Lett. 2006 Mar 15;16(6):1621-7. Epub 2006 Jan 4. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/16387495 16387495]
Crystal structure of the hepatitis C virus NS3 protease domain complexed with a synthetic NS4A cofactor peptide., Kim JL, Morgenstern KA, Lin C, Fox T, Dwyer MD, Landro JA, Chambers SP, Markland W, Lepre CA, O'Malley ET, Harbeson SL, Rice CM, Murcko MA, Caron PR, Thomson JA, Cell. 1996 Oct 18;87(2):343-55. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/8861917 8861917]
Hepatitis C virus NS3-4A serine protease inhibitors: use of a P2-P1 cyclopropyl alanine combination for improved potency., Bogen S, Saksena AK, Arasappan A, Gu H, Njoroge FG, Girijavallabhan V, Pichardo J, Butkiewicz N, Prongay A, Madison V, Bioorg Med Chem Lett. 2005 Oct 15;15(20):4515-9. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/16112862 16112862]
Design and synthesis of depeptidized macrocyclic inhibitors of hepatitis C NS3-4A protease using structure-based drug design., Venkatraman S, Njoroge FG, Girijavallabhan VM, Madison VS, Yao NH, Prongay AJ, Butkiewicz N, Pichardo J, J Med Chem. 2005 Aug 11;48(16):5088-91. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/16078825 16078825]
Proline-based macrocyclic inhibitors of the hepatitis C virus: stereoselective synthesis and biological activity., Chen KX, Njoroge FG, Vibulbhan B, Prongay A, Pichardo J, Madison V, Buevich A, Chan TM, Angew Chem Int Ed Engl. 2005 Nov 4;44(43):7024-8. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/16211639 16211639]
Novel 2-oxoimidazolidine-4-carboxylic acid derivatives as hepatitis C virus NS3-4A serine protease inhibitors: synthesis, activity, and X-ray crystal structure of an enzyme inhibitor complex., Arasappan A, Njoroge FG, Parekh TN, Yang X, Pichardo J, Butkiewicz N, Prongay A, Yao N, Girijavallabhan V, Bioorg Med Chem Lett. 2004 Dec 6;14(23):5751-5. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/15501035 15501035]
[[Category: Hepatitis c virus]]
[[Category: Hepatitis c virus]]
[[Category: Protein complex]]
[[Category: Protein complex]]
Line 36: Line 50:
[[Category: Ketoamide inhibitor]]
[[Category: Ketoamide inhibitor]]
[[Category: Ns3 protease]]
[[Category: Ns3 protease]]
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May  4 03:38:32 2008''
 
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jul 28 20:39:28 2008''

Revision as of 20:39, 28 July 2008

File:2f9v.png

Template:STRUCTURE 2f9v

HCV NS3 protease domain with NS4a peptide and a ketoamide inhibitor with P1 and P2 cyclopropylalanninesHCV NS3 protease domain with NS4a peptide and a ketoamide inhibitor with P1 and P2 cyclopropylalannines

Template:ABSTRACT PUBMED 16387495

About this StructureAbout this Structure

2F9V is a Protein complex structure of sequences from Hepatitis c virus. Full crystallographic information is available from OCA.

ReferenceReference

Depeptidization efforts on P3-P2' alpha-ketoamide inhibitors of HCV NS3-4A serine protease: effect on HCV replicon activity., Bogen SL, Ruan S, Liu R, Agrawal S, Pichardo J, Prongay A, Baroudy B, Saksena AK, Girijavallabhan V, Njoroge FG, Bioorg Med Chem Lett. 2006 Mar 15;16(6):1621-7. Epub 2006 Jan 4. PMID:16387495

Crystal structure of the hepatitis C virus NS3 protease domain complexed with a synthetic NS4A cofactor peptide., Kim JL, Morgenstern KA, Lin C, Fox T, Dwyer MD, Landro JA, Chambers SP, Markland W, Lepre CA, O'Malley ET, Harbeson SL, Rice CM, Murcko MA, Caron PR, Thomson JA, Cell. 1996 Oct 18;87(2):343-55. PMID:8861917

Hepatitis C virus NS3-4A serine protease inhibitors: use of a P2-P1 cyclopropyl alanine combination for improved potency., Bogen S, Saksena AK, Arasappan A, Gu H, Njoroge FG, Girijavallabhan V, Pichardo J, Butkiewicz N, Prongay A, Madison V, Bioorg Med Chem Lett. 2005 Oct 15;15(20):4515-9. PMID:16112862

Design and synthesis of depeptidized macrocyclic inhibitors of hepatitis C NS3-4A protease using structure-based drug design., Venkatraman S, Njoroge FG, Girijavallabhan VM, Madison VS, Yao NH, Prongay AJ, Butkiewicz N, Pichardo J, J Med Chem. 2005 Aug 11;48(16):5088-91. PMID:16078825

Proline-based macrocyclic inhibitors of the hepatitis C virus: stereoselective synthesis and biological activity., Chen KX, Njoroge FG, Vibulbhan B, Prongay A, Pichardo J, Madison V, Buevich A, Chan TM, Angew Chem Int Ed Engl. 2005 Nov 4;44(43):7024-8. PMID:16211639

Novel 2-oxoimidazolidine-4-carboxylic acid derivatives as hepatitis C virus NS3-4A serine protease inhibitors: synthesis, activity, and X-ray crystal structure of an enzyme inhibitor complex., Arasappan A, Njoroge FG, Parekh TN, Yang X, Pichardo J, Butkiewicz N, Prongay A, Yao N, Girijavallabhan V, Bioorg Med Chem Lett. 2004 Dec 6;14(23):5751-5. PMID:15501035

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