2q1j: Difference between revisions

Revision as of 14:10, 4 May 2008

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.

About this StructureAbout this Structure

2Q1J is a Protein complex structure of sequences from Homo sapiens. 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 Sun May 4 14:10:17 2008

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

OCA

@@ Line 1: / Line 1: @@
 [[Image:2q1j.jpg|left|200px]]
- {{Structure
+<!--
-|PDB= 2q1j |SIZE=350|CAPTION= <scene name='initialview01'>2q1j</scene>, resolution 1.90&Aring;
+The line below this paragraph, containing "STRUCTURE_2q1j", creates the "Structure Box" on the page.
-|SITE=
+You may change the PDB parameter (which sets the PDB file loaded into the applet)
-|LIGAND= <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=FXI:1-(BUTYL{[(4-CHLOROPHENYL)AMINO]CARBONYL}AMINO)-N-[3-FLUORO-2&#39;-(METHYLSULFONYL)BIPHENYL-4-YL]CYCLOPROPANECARBOXAMIDE'>FXI</scene>
+or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
-|ACTIVITY= <span class='plainlinks'>[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] </span>
+or leave the SCENE parameter empty for the default display.
-|GENE=
+-->
-|DOMAIN=
+{{STRUCTURE_2q1j|  PDB=2q1j  |  SCENE=  }}
-|RELATEDENTRY=
-|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2q1j FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2q1j OCA], [http://www.ebi.ac.uk/pdbsum/2q1j PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2q1j RCSB]</span>
-}}
 '''The discovery of glycine and related amino acid-based factor xa inhibitors'''
@@ Line 32: / Line 29: @@
 [[Category: Kohrt, J T.]]
 [[Category: Zhang, E.]]
-[[Category: blood coagulation]]
+[[Category: Blood coagulation]]
-[[Category: calcium]]
+[[Category: Calcium]]
-[[Category: cleavage on pair of basic residue]]
+[[Category: Cleavage on pair of basic residue]]
-[[Category: coagulation fxa]]
+[[Category: Coagulation fxa]]
-[[Category: egf-like domain]]
+[[Category: Egf-like domain]]
-[[Category: gamma-carboxyglutamic acid]]
+[[Category: Gamma-carboxyglutamic acid]]
-[[Category: glycoprotein]]
+[[Category: Glycoprotein]]
-[[Category: hydrolase]]
+[[Category: Hydrolase]]
-[[Category: hydroxylation]]
+[[Category: Hydroxylation]]
-[[Category: polymorphism]]
+[[Category: Polymorphism]]
-[[Category: protease]]
+[[Category: Protease]]
-[[Category: serine protease]]
+[[Category: Serine protease]]
-[[Category: zymogen]]
+[[Category: Zymogen]]
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May  4 14:10:17 2008''
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 04:43:23 2008''