1sb1: Difference between revisions

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[[Image:1sb1.gif|left|200px]]<br />

[[Image:1sb1.gif|left|200px]]<br /><applet load="1sb1" size="350" color="white" frame="true" align="right" spinBox="true"

<applet load="1sb1" size="~~450~~" color="white" frame="true" align="right" spinBox="true"

caption="1sb1, resolution 1.90Å" />

'''Novel Non-Covalent Thrombin Inhibitors Incorporating P1 4,5,6,7-Tetrahydrobenzothiazole Arginine Side Chain Mimetics'''<br />

==Overview==

The design, synthesis and biological activity of a series of novel, non-covalent D-Phe-Pro-Arg motif-based thrombin inhibitors incorporating, 4,5,6,7-tetrahydrobenzothiazol-2-amine as a novel arginine surrogate are, described. Compound 9, the most potent in the series of thrombin, inhibitors, exhibited an in vitro K(i) of 128 nM and 342-fold selectivity, against trypsin. The binding mode of this novel class of thrombin, inhibitors in the enzyme active site, based on the X-ray crystal structure, of compound 9 co-crystallized with human alpha-thrombin, is discussed.

The design, synthesis and biological activity of a series of novel non-covalent D-Phe-Pro-Arg motif-based thrombin inhibitors incorporating 4,5,6,7-tetrahydrobenzothiazol-2-amine as a novel arginine surrogate are described. Compound 9, the most potent in the series of thrombin inhibitors, exhibited an in vitro K(i) of 128 nM and 342-fold selectivity against trypsin. The binding mode of this novel class of thrombin inhibitors in the enzyme active site, based on the X-ray crystal structure of compound 9 co-crystallized with human alpha-thrombin, is discussed.

==Disease==

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==About this Structure==

1SB1 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 NA and 165 as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Thrombin Thrombin], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.21.5 3.4.21.5] Full crystallographic information is available from [http://~~ispc~~.weizmann.ac.il/oca-bin/ocashort?id=1SB1 OCA].

1SB1 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=NA:'>NA</scene> and <scene name='pdbligand=165:'>165</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Thrombin Thrombin], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.21.5 3.4.21.5] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1SB1 OCA].

==Reference==

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[[Category: thrombin; inhibition; hirugen; serine protease inhibitor]]

''Page seeded by [http://~~ispc~~.weizmann.ac.il/oca OCA ] on ~~Mon Nov 12 19~~:12:~~14 2007~~''

''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 14:59:40 2008''

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@@ Line 1: / Line 1: @@
-[[Image:1sb1.gif|left|200px]]<br />
+[[Image:1sb1.gif|left|200px]]<br /><applet load="1sb1" size="350" color="white" frame="true" align="right" spinBox="true"
-<applet load="1sb1" size="450" color="white" frame="true" align="right" spinBox="true"
 caption="1sb1, resolution 1.90&Aring;" />
 '''Novel Non-Covalent Thrombin Inhibitors Incorporating P1 4,5,6,7-Tetrahydrobenzothiazole Arginine Side Chain Mimetics'''<br />
 ==Overview==
-The design, synthesis and biological activity of a series of novel, non-covalent D-Phe-Pro-Arg motif-based thrombin inhibitors incorporating, 4,5,6,7-tetrahydrobenzothiazol-2-amine as a novel arginine surrogate are, described. Compound 9, the most potent in the series of thrombin, inhibitors, exhibited an in vitro K(i) of 128 nM and 342-fold selectivity, against trypsin. The binding mode of this novel class of thrombin, inhibitors in the enzyme active site, based on the X-ray crystal structure, of compound 9 co-crystallized with human alpha-thrombin, is discussed.
+The design, synthesis and biological activity of a series of novel non-covalent D-Phe-Pro-Arg motif-based thrombin inhibitors incorporating 4,5,6,7-tetrahydrobenzothiazol-2-amine as a novel arginine surrogate are described. Compound 9, the most potent in the series of thrombin inhibitors, exhibited an in vitro K(i) of 128 nM and 342-fold selectivity against trypsin. The binding mode of this novel class of thrombin inhibitors in the enzyme active site, based on the X-ray crystal structure of compound 9 co-crystallized with human alpha-thrombin, is discussed.
 ==Disease==
@@ Line 11: / Line 10: @@
 ==About this Structure==
-SB1 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 NA and 165 as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Thrombin Thrombin], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.21.5 3.4.21.5] Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1SB1 OCA].
+SB1 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=NA:'>NA</scene> and <scene name='pdbligand=165:'>165</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Thrombin Thrombin], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.21.5 3.4.21.5] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1SB1 OCA].
 ==Reference==
@@ Line 30: / Line 29: @@
 [[Category: thrombin; inhibition; hirugen; serine protease inhibitor]]
-''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 12 19:12:14 2007''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 14:59:40 2008''