Sean Swale/Human Thrombin Inhibitor - Revision history

http://52.214.119.220/wiki/index.php?action=history&feed=atom&title=Sean_Swale%2FHuman_Thrombin_Inhibitor Sean Swale/Human Thrombin Inhibitor - Revision history 2026-04-14T18:32:06Z Revision history for this page on the wiki MediaWiki 1.11.2 http://52.214.119.220/wiki/index.php?title=Sean_Swale/Human_Thrombin_Inhibitor&diff=1820471&oldid=prev Michal Harel at 10:08, 14 July 2013 2013-07-14T10:08:00Z

<p></p> <table style="background-color: white; color:black;"> <col class='diff-marker' /> <col class='diff-content' /> <col class='diff-marker' /> <col class='diff-content' /> <tr> <td colspan='2' style="background-color: white; color:black;">←Older revision</td> <td colspan='2' style="background-color: white; color:black;">Revision as of 10:08, 14 July 2013</td> </tr> <tr><td colspan="2" class="diff-lineno">Line 1:</td> <td colspan="2" class="diff-lineno">Line 1:</td></tr> <tr><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"></td><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"></td></tr> <tr><td class='diff-marker'>-</td><td style="background: #ffa; color:black; font-size: smaller;"><div> </div></td><td class='diff-marker'>+</td><td style="background: #cfc; color:black; font-size: smaller;"><div>{{STRUCTURE_3utu| PDB=3utu | SIZE=400| SCENE= |right|CAPTION=Human Thrombin, <ins style="color: red; font-weight: bold; text-decoration: none;">heavy chain (red), light chain (aqua) complex with hirudin (gold), pyrrolidine derivative and Na+ ion </ins>[[3utu]] }}</div></td></tr> <tr><td class='diff-marker'>-</td><td style="background: #ffa; color:black; font-size: smaller;"><div>{{STRUCTURE_3utu| PDB=3utu | SIZE=400| SCENE= |right|CAPTION=Human Thrombin, [[3utu]] }}</div></td><td class='diff-marker'>+</td><td style="background: #cfc; color:black; font-size: smaller;"><div></div></td></tr> <tr><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"></td><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"></td></tr> <tr><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"><div>===Reasons to develop another <scene name='Sean_Swale/Human_Thrombin_Inhibitor/Active_site/3'>Thrombin</scene> Inhibitor===</div></td><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"><div>===Reasons to develop another <scene name='Sean_Swale/Human_Thrombin_Inhibitor/Active_site/3'>Thrombin</scene> Inhibitor===</div></td></tr> </table>

Michal Harel http://52.214.119.220/wiki/index.php?title=Sean_Swale/Human_Thrombin_Inhibitor&diff=1744956&oldid=prev Michal Harel at 12:10, 18 March 2013 2013-03-18T12:10:34Z

<p></p> <table style="background-color: white; color:black;"> <col class='diff-marker' /> <col class='diff-content' /> <col class='diff-marker' /> <col class='diff-content' /> <tr> <td colspan='2' style="background-color: white; color:black;">←Older revision</td> <td colspan='2' style="background-color: white; color:black;">Revision as of 12:10, 18 March 2013</td> </tr> <tr><td colspan="2" class="diff-lineno">Line 1:</td> <td colspan="2" class="diff-lineno">Line 1:</td></tr> <tr><td class='diff-marker'>-</td><td style="background: #ffa; color:black; font-size: smaller;"><div><del style="color: red; font-weight: bold; text-decoration: none;"><StructureSection load='3utu' size='500' frame='false' align='right' caption='Human Thrombin, [[3utu]]' scene=''></del></div></td><td class='diff-marker'>+</td><td style="background: #cfc; color:black; font-size: smaller;"><div> </div></td></tr> <tr><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"></td><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"></td></tr> <tr><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"><div>{{STRUCTURE_3utu| PDB=3utu | SIZE=400| SCENE= |right|CAPTION=Human Thrombin, [[3utu]] }}</div></td><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"><div>{{STRUCTURE_3utu| PDB=3utu | SIZE=400| SCENE= |right|CAPTION=Human Thrombin, [[3utu]] }}</div></td></tr> </table>

Michal Harel http://52.214.119.220/wiki/index.php?title=Sean_Swale/Human_Thrombin_Inhibitor&diff=1744945&oldid=prev Michal Harel at 12:09, 18 March 2013 2013-03-18T12:09:55Z

<p></p> <table style="background-color: white; color:black;"> <col class='diff-marker' /> <col class='diff-content' /> <col class='diff-marker' /> <col class='diff-content' /> <tr> <td colspan='2' style="background-color: white; color:black;">←Older revision</td> <td colspan='2' style="background-color: white; color:black;">Revision as of 12:09, 18 March 2013</td> </tr> <tr><td colspan="2" class="diff-lineno">Line 1:</td> <td colspan="2" class="diff-lineno">Line 1:</td></tr> <tr><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"><div><StructureSection load='3utu' size='500' frame='false' align='right' caption='Human Thrombin, [[3utu]]' scene=''></div></td><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"><div><StructureSection load='3utu' size='500' frame='false' align='right' caption='Human Thrombin, [[3utu]]' scene=''></div></td></tr> <tr><td colspan="2"> </td><td class='diff-marker'>+</td><td style="background: #cfc; color:black; font-size: smaller;"></td></tr> <tr><td colspan="2"> </td><td class='diff-marker'>+</td><td style="background: #cfc; color:black; font-size: smaller;"><div>{{STRUCTURE_3utu| PDB=3utu | SIZE=400| SCENE= |right|CAPTION=Human Thrombin, [[3utu]] }}</div></td></tr> <tr><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"></td><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"></td></tr> <tr><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"><div>===Reasons to develop another <scene name='Sean_Swale/Human_Thrombin_Inhibitor/Active_site/3'>Thrombin</scene> Inhibitor===</div></td><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"><div>===Reasons to develop another <scene name='Sean_Swale/Human_Thrombin_Inhibitor/Active_site/3'>Thrombin</scene> Inhibitor===</div></td></tr> </table>

Michal Harel http://52.214.119.220/wiki/index.php?title=Sean_Swale/Human_Thrombin_Inhibitor&diff=1744934&oldid=prev Michal Harel at 12:07, 18 March 2013 2013-03-18T12:07:01Z

<p></p> <table style="background-color: white; color:black;"> <col class='diff-marker' /> <col class='diff-content' /> <col class='diff-marker' /> <col class='diff-content' /> <tr> <td colspan='2' style="background-color: white; color:black;">←Older revision</td> <td colspan='2' style="background-color: white; color:black;">Revision as of 12:07, 18 March 2013</td> </tr> <tr><td colspan="2" class="diff-lineno">Line 1:</td> <td colspan="2" class="diff-lineno">Line 1:</td></tr> <tr><td class='diff-marker'>-</td><td style="background: #ffa; color:black; font-size: smaller;"><div><StructureSection load='3utu' size='500' frame='false' align='right' <del style="color: red; font-weight: bold; text-decoration: none;">|</del>caption='Human Thrombin, [[3utu]]' scene=''></div></td><td class='diff-marker'>+</td><td style="background: #cfc; color:black; font-size: smaller;"><div><StructureSection load='3utu' size='500' frame='false' align='right' caption='Human Thrombin, [[3utu]]' scene=''></div></td></tr> <tr><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"></td><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"></td></tr> <tr><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"><div>===Reasons to develop another <scene name='Sean_Swale/Human_Thrombin_Inhibitor/Active_site/3'>Thrombin</scene> Inhibitor===</div></td><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"><div>===Reasons to develop another <scene name='Sean_Swale/Human_Thrombin_Inhibitor/Active_site/3'>Thrombin</scene> Inhibitor===</div></td></tr> </table>

Michal Harel http://52.214.119.220/wiki/index.php?title=Sean_Swale/Human_Thrombin_Inhibitor&diff=1744933&oldid=prev Michal Harel at 12:05, 18 March 2013 2013-03-18T12:05:21Z

<p></p> <table style="background-color: white; color:black;"> <col class='diff-marker' /> <col class='diff-content' /> <col class='diff-marker' /> <col class='diff-content' /> <tr> <td colspan='2' style="background-color: white; color:black;">←Older revision</td> <td colspan='2' style="background-color: white; color:black;">Revision as of 12:05, 18 March 2013</td> </tr> <tr><td colspan="2" class="diff-lineno">Line 1:</td> <td colspan="2" class="diff-lineno">Line 1:</td></tr> <tr><td class='diff-marker'>-</td><td style="background: #ffa; color:black; font-size: smaller;"><div><StructureSection load='3utu' size='500' frame='false' align='right' |caption='Human Thrombin' scene=''></div></td><td class='diff-marker'>+</td><td style="background: #cfc; color:black; font-size: smaller;"><div><StructureSection load='3utu' size='500' frame='false' align='right' |caption='Human Thrombin<ins style="color: red; font-weight: bold; text-decoration: none;">, [[3utu]]</ins>' scene=''></div></td></tr> <tr><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"></td><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"></td></tr> <tr><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"><div>===Reasons to develop another <scene name='Sean_Swale/Human_Thrombin_Inhibitor/Active_site/3'>Thrombin</scene> Inhibitor===</div></td><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"><div>===Reasons to develop another <scene name='Sean_Swale/Human_Thrombin_Inhibitor/Active_site/3'>Thrombin</scene> Inhibitor===</div></td></tr> </table>

Michal Harel http://52.214.119.220/wiki/index.php?title=Sean_Swale/Human_Thrombin_Inhibitor&diff=1609295&oldid=prev Sean Swale at 20:18, 16 November 2012 2012-11-16T20:18:43Z

<p></p> <table style="background-color: white; color:black;"> <col class='diff-marker' /> <col class='diff-content' /> <col class='diff-marker' /> <col class='diff-content' /> <tr> <td colspan='2' style="background-color: white; color:black;">←Older revision</td> <td colspan='2' style="background-color: white; color:black;">Revision as of 20:18, 16 November 2012</td> </tr> <tr><td colspan="2" class="diff-lineno">Line 8:</td> <td colspan="2" class="diff-lineno">Line 8:</td></tr> <tr><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"><div>===Phe-Pro-p-amidinobenzylamine===</div></td><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"><div>===Phe-Pro-p-amidinobenzylamine===</div></td></tr> <tr><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"><div>An early experiment to find a better thrombin inhibitor yielded a structure that was able to bond to the P1 and P2 sites of Thrombin effectively. In 1996 Lilly research laboratories created D-Phe-Pro-p-amidinobenzylamine by making improvements on the previous structure D-Phe-Pro-Agmatine. The new compound they created bonded to thrombin 130x more than it did to trypsin (also a serine protease), and it was highly selective of thrombin over fibrinolytic enzymes which break down fibrin clots. The inhibitor bound with Thrombin at rates 26,000x greater than with plasmin,<ref> http://voices.yahoo.com/what-fibrinolytic-enzymes-6186058.html?cat=68</ref>, 170,000x greater than with t-Pa, and 400,000x greater than with urokinase. </div></td><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"><div>An early experiment to find a better thrombin inhibitor yielded a structure that was able to bond to the P1 and P2 sites of Thrombin effectively. In 1996 Lilly research laboratories created D-Phe-Pro-p-amidinobenzylamine by making improvements on the previous structure D-Phe-Pro-Agmatine. The new compound they created bonded to thrombin 130x more than it did to trypsin (also a serine protease), and it was highly selective of thrombin over fibrinolytic enzymes which break down fibrin clots. The inhibitor bound with Thrombin at rates 26,000x greater than with plasmin,<ref> http://voices.yahoo.com/what-fibrinolytic-enzymes-6186058.html?cat=68</ref>, 170,000x greater than with t-Pa, and 400,000x greater than with urokinase. </div></td></tr> <tr><td class='diff-marker'>-</td><td style="background: #ffa; color:black; font-size: smaller;"><div>[[Image:1996 inhibitor rates.png|left|100|Inhibitor 12 is the identical P1 and P2 sites of Inhibitor 65.(1996)<ref> M. R. Wiley, N. Y. Chirgadze, D. K. Clawson, T. J. Craft, D. S. GiffordMoore, N. D. Jones, J. L. Olkowski, L. C. Weir, G. F. Smith, Bioorg. Med. Chem. Lett. 1996, 6, 2387. http://www.sciencedirect.com/science/article/pii/0960894X96004428 </ref>]]</div></td><td class='diff-marker'>+</td><td style="background: #cfc; color:black; font-size: smaller;"><div>[[Image:1996 inhibitor rates.png|left<ins style="color: red; font-weight: bold; text-decoration: none;">|frame</ins>|100|Inhibitor 12 is the identical P1 and P2 sites of Inhibitor 65.(1996)<ref> M. R. Wiley, N. Y. Chirgadze, D. K. Clawson, T. J. Craft, D. S. GiffordMoore, N. D. Jones, J. L. Olkowski, L. C. Weir, G. F. Smith, Bioorg. Med. Chem. Lett. 1996, 6, 2387. http://www.sciencedirect.com/science/article/pii/0960894X96004428 </ref>]]</div></td></tr> <tr><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"><div>Its selectivity was gained by binding its nitrogens on the benzamidine <scene name='Sean_Swale/Human_Thrombin_Inhibitor/P1_residue/1'>group</scene> by hydrogen bonding to Asp 189, and by fitting its benzamidine benzene into a hydrophobic pocket with Ser 214-Glu 217 and Asp 189-Glu 192 on the other side. The <scene name='Sean_Swale/Human_Thrombin_Inhibitor/P2_proline/1'>proline</scene> residue is in another hydrophobic pocket made up of His 57, Tyr 60A, Leu 99, and Trp 60D. The rest of this structure is unimportant on review of inhibitor 65 because only the amidinobenzylamine which occupies R1 and the proline which occupies the R2 sit are the same residues on inhibitor 65.<ref> M. R. Wiley, N. Y. Chirgadze, D. K. Clawson, T. J. Craft, D. S. GiffordMoore, N. D. Jones, J. L. Olkowski, L. C. Weir, G. F. Smith, Bioorg. Med. Chem. Lett. 1996, 6, 2387. http://www.sciencedirect.com/science/article/pii/0960894X96004428 </ref></div></td><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"><div>Its selectivity was gained by binding its nitrogens on the benzamidine <scene name='Sean_Swale/Human_Thrombin_Inhibitor/P1_residue/1'>group</scene> by hydrogen bonding to Asp 189, and by fitting its benzamidine benzene into a hydrophobic pocket with Ser 214-Glu 217 and Asp 189-Glu 192 on the other side. The <scene name='Sean_Swale/Human_Thrombin_Inhibitor/P2_proline/1'>proline</scene> residue is in another hydrophobic pocket made up of His 57, Tyr 60A, Leu 99, and Trp 60D. The rest of this structure is unimportant on review of inhibitor 65 because only the amidinobenzylamine which occupies R1 and the proline which occupies the R2 sit are the same residues on inhibitor 65.<ref> M. R. Wiley, N. Y. Chirgadze, D. K. Clawson, T. J. Craft, D. S. GiffordMoore, N. D. Jones, J. L. Olkowski, L. C. Weir, G. F. Smith, Bioorg. Med. Chem. Lett. 1996, 6, 2387. http://www.sciencedirect.com/science/article/pii/0960894X96004428 </ref></div></td></tr> <tr><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"></td><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"></td></tr> </table>

Sean Swale http://52.214.119.220/wiki/index.php?title=Sean_Swale/Human_Thrombin_Inhibitor&diff=1609294&oldid=prev Sean Swale at 20:17, 16 November 2012 2012-11-16T20:17:59Z

<p></p> <table style="background-color: white; color:black;"> <col class='diff-marker' /> <col class='diff-content' /> <col class='diff-marker' /> <col class='diff-content' /> <tr> <td colspan='2' style="background-color: white; color:black;">←Older revision</td> <td colspan='2' style="background-color: white; color:black;">Revision as of 20:17, 16 November 2012</td> </tr> <tr><td colspan="2" class="diff-lineno">Line 8:</td> <td colspan="2" class="diff-lineno">Line 8:</td></tr> <tr><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"><div>===Phe-Pro-p-amidinobenzylamine===</div></td><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"><div>===Phe-Pro-p-amidinobenzylamine===</div></td></tr> <tr><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"><div>An early experiment to find a better thrombin inhibitor yielded a structure that was able to bond to the P1 and P2 sites of Thrombin effectively. In 1996 Lilly research laboratories created D-Phe-Pro-p-amidinobenzylamine by making improvements on the previous structure D-Phe-Pro-Agmatine. The new compound they created bonded to thrombin 130x more than it did to trypsin (also a serine protease), and it was highly selective of thrombin over fibrinolytic enzymes which break down fibrin clots. The inhibitor bound with Thrombin at rates 26,000x greater than with plasmin,<ref> http://voices.yahoo.com/what-fibrinolytic-enzymes-6186058.html?cat=68</ref>, 170,000x greater than with t-Pa, and 400,000x greater than with urokinase. </div></td><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"><div>An early experiment to find a better thrombin inhibitor yielded a structure that was able to bond to the P1 and P2 sites of Thrombin effectively. In 1996 Lilly research laboratories created D-Phe-Pro-p-amidinobenzylamine by making improvements on the previous structure D-Phe-Pro-Agmatine. The new compound they created bonded to thrombin 130x more than it did to trypsin (also a serine protease), and it was highly selective of thrombin over fibrinolytic enzymes which break down fibrin clots. The inhibitor bound with Thrombin at rates 26,000x greater than with plasmin,<ref> http://voices.yahoo.com/what-fibrinolytic-enzymes-6186058.html?cat=68</ref>, 170,000x greater than with t-Pa, and 400,000x greater than with urokinase. </div></td></tr> <tr><td class='diff-marker'>-</td><td style="background: #ffa; color:black; font-size: smaller;"><div>[[Image:1996 inhibitor rates.png|left|<del style="color: red; font-weight: bold; text-decoration: none;">50|frame</del>|Inhibitor 12 is the identical P1 and P2 sites of Inhibitor 65.(1996)<ref> M. R. Wiley, N. Y. Chirgadze, D. K. Clawson, T. J. Craft, D. S. GiffordMoore, N. D. Jones, J. L. Olkowski, L. C. Weir, G. F. Smith, Bioorg. Med. Chem. Lett. 1996, 6, 2387. http://www.sciencedirect.com/science/article/pii/0960894X96004428 </ref>]]</div></td><td class='diff-marker'>+</td><td style="background: #cfc; color:black; font-size: smaller;"><div>[[Image:1996 inhibitor rates.png|left|<ins style="color: red; font-weight: bold; text-decoration: none;">100</ins>|Inhibitor 12 is the identical P1 and P2 sites of Inhibitor 65.(1996)<ref> M. R. Wiley, N. Y. Chirgadze, D. K. Clawson, T. J. Craft, D. S. GiffordMoore, N. D. Jones, J. L. Olkowski, L. C. Weir, G. F. Smith, Bioorg. Med. Chem. Lett. 1996, 6, 2387. http://www.sciencedirect.com/science/article/pii/0960894X96004428 </ref>]]</div></td></tr> <tr><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"><div>Its selectivity was gained by binding its nitrogens on the benzamidine <scene name='Sean_Swale/Human_Thrombin_Inhibitor/P1_residue/1'>group</scene> by hydrogen bonding to Asp 189, and by fitting its benzamidine benzene into a hydrophobic pocket with Ser 214-Glu 217 and Asp 189-Glu 192 on the other side. The <scene name='Sean_Swale/Human_Thrombin_Inhibitor/P2_proline/1'>proline</scene> residue is in another hydrophobic pocket made up of His 57, Tyr 60A, Leu 99, and Trp 60D. The rest of this structure is unimportant on review of inhibitor 65 because only the amidinobenzylamine which occupies R1 and the proline which occupies the R2 sit are the same residues on inhibitor 65.<ref> M. R. Wiley, N. Y. Chirgadze, D. K. Clawson, T. J. Craft, D. S. GiffordMoore, N. D. Jones, J. L. Olkowski, L. C. Weir, G. F. Smith, Bioorg. Med. Chem. Lett. 1996, 6, 2387. http://www.sciencedirect.com/science/article/pii/0960894X96004428 </ref></div></td><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"><div>Its selectivity was gained by binding its nitrogens on the benzamidine <scene name='Sean_Swale/Human_Thrombin_Inhibitor/P1_residue/1'>group</scene> by hydrogen bonding to Asp 189, and by fitting its benzamidine benzene into a hydrophobic pocket with Ser 214-Glu 217 and Asp 189-Glu 192 on the other side. The <scene name='Sean_Swale/Human_Thrombin_Inhibitor/P2_proline/1'>proline</scene> residue is in another hydrophobic pocket made up of His 57, Tyr 60A, Leu 99, and Trp 60D. The rest of this structure is unimportant on review of inhibitor 65 because only the amidinobenzylamine which occupies R1 and the proline which occupies the R2 sit are the same residues on inhibitor 65.<ref> M. R. Wiley, N. Y. Chirgadze, D. K. Clawson, T. J. Craft, D. S. GiffordMoore, N. D. Jones, J. L. Olkowski, L. C. Weir, G. F. Smith, Bioorg. Med. Chem. Lett. 1996, 6, 2387. http://www.sciencedirect.com/science/article/pii/0960894X96004428 </ref></div></td></tr> <tr><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"></td><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"></td></tr> </table>

Sean Swale http://52.214.119.220/wiki/index.php?title=Sean_Swale/Human_Thrombin_Inhibitor&diff=1609293&oldid=prev Sean Swale at 20:17, 16 November 2012 2012-11-16T20:17:01Z

<p></p> <table style="background-color: white; color:black;"> <col class='diff-marker' /> <col class='diff-content' /> <col class='diff-marker' /> <col class='diff-content' /> <tr> <td colspan='2' style="background-color: white; color:black;">←Older revision</td> <td colspan='2' style="background-color: white; color:black;">Revision as of 20:17, 16 November 2012</td> </tr> <tr><td colspan="2" class="diff-lineno">Line 8:</td> <td colspan="2" class="diff-lineno">Line 8:</td></tr> <tr><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"><div>===Phe-Pro-p-amidinobenzylamine===</div></td><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"><div>===Phe-Pro-p-amidinobenzylamine===</div></td></tr> <tr><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"><div>An early experiment to find a better thrombin inhibitor yielded a structure that was able to bond to the P1 and P2 sites of Thrombin effectively. In 1996 Lilly research laboratories created D-Phe-Pro-p-amidinobenzylamine by making improvements on the previous structure D-Phe-Pro-Agmatine. The new compound they created bonded to thrombin 130x more than it did to trypsin (also a serine protease), and it was highly selective of thrombin over fibrinolytic enzymes which break down fibrin clots. The inhibitor bound with Thrombin at rates 26,000x greater than with plasmin,<ref> http://voices.yahoo.com/what-fibrinolytic-enzymes-6186058.html?cat=68</ref>, 170,000x greater than with t-Pa, and 400,000x greater than with urokinase. </div></td><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"><div>An early experiment to find a better thrombin inhibitor yielded a structure that was able to bond to the P1 and P2 sites of Thrombin effectively. In 1996 Lilly research laboratories created D-Phe-Pro-p-amidinobenzylamine by making improvements on the previous structure D-Phe-Pro-Agmatine. The new compound they created bonded to thrombin 130x more than it did to trypsin (also a serine protease), and it was highly selective of thrombin over fibrinolytic enzymes which break down fibrin clots. The inhibitor bound with Thrombin at rates 26,000x greater than with plasmin,<ref> http://voices.yahoo.com/what-fibrinolytic-enzymes-6186058.html?cat=68</ref>, 170,000x greater than with t-Pa, and 400,000x greater than with urokinase. </div></td></tr> <tr><td class='diff-marker'>-</td><td style="background: #ffa; color:black; font-size: smaller;"><div>[[Image:1996 inhibitor rates.png|left|<del style="color: red; font-weight: bold; text-decoration: none;">100</del>|frame|Inhibitor 12 is the identical P1 and P2 sites of Inhibitor 65.(1996)<ref> M. R. Wiley, N. Y. Chirgadze, D. K. Clawson, T. J. Craft, D. S. GiffordMoore, N. D. Jones, J. L. Olkowski, L. C. Weir, G. F. Smith, Bioorg. Med. Chem. Lett. 1996, 6, 2387. http://www.sciencedirect.com/science/article/pii/0960894X96004428 </ref>]]</div></td><td class='diff-marker'>+</td><td style="background: #cfc; color:black; font-size: smaller;"><div>[[Image:1996 inhibitor rates.png|left|<ins style="color: red; font-weight: bold; text-decoration: none;">50</ins>|frame|Inhibitor 12 is the identical P1 and P2 sites of Inhibitor 65.(1996)<ref> M. R. Wiley, N. Y. Chirgadze, D. K. Clawson, T. J. Craft, D. S. GiffordMoore, N. D. Jones, J. L. Olkowski, L. C. Weir, G. F. Smith, Bioorg. Med. Chem. Lett. 1996, 6, 2387. http://www.sciencedirect.com/science/article/pii/0960894X96004428 </ref>]]</div></td></tr> <tr><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"><div>Its selectivity was gained by binding its nitrogens on the benzamidine <scene name='Sean_Swale/Human_Thrombin_Inhibitor/P1_residue/1'>group</scene> by hydrogen bonding to Asp 189, and by fitting its benzamidine benzene into a hydrophobic pocket with Ser 214-Glu 217 and Asp 189-Glu 192 on the other side. The <scene name='Sean_Swale/Human_Thrombin_Inhibitor/P2_proline/1'>proline</scene> residue is in another hydrophobic pocket made up of His 57, Tyr 60A, Leu 99, and Trp 60D. The rest of this structure is unimportant on review of inhibitor 65 because only the amidinobenzylamine which occupies R1 and the proline which occupies the R2 sit are the same residues on inhibitor 65.<ref> M. R. Wiley, N. Y. Chirgadze, D. K. Clawson, T. J. Craft, D. S. GiffordMoore, N. D. Jones, J. L. Olkowski, L. C. Weir, G. F. Smith, Bioorg. Med. Chem. Lett. 1996, 6, 2387. http://www.sciencedirect.com/science/article/pii/0960894X96004428 </ref></div></td><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"><div>Its selectivity was gained by binding its nitrogens on the benzamidine <scene name='Sean_Swale/Human_Thrombin_Inhibitor/P1_residue/1'>group</scene> by hydrogen bonding to Asp 189, and by fitting its benzamidine benzene into a hydrophobic pocket with Ser 214-Glu 217 and Asp 189-Glu 192 on the other side. The <scene name='Sean_Swale/Human_Thrombin_Inhibitor/P2_proline/1'>proline</scene> residue is in another hydrophobic pocket made up of His 57, Tyr 60A, Leu 99, and Trp 60D. The rest of this structure is unimportant on review of inhibitor 65 because only the amidinobenzylamine which occupies R1 and the proline which occupies the R2 sit are the same residues on inhibitor 65.<ref> M. R. Wiley, N. Y. Chirgadze, D. K. Clawson, T. J. Craft, D. S. GiffordMoore, N. D. Jones, J. L. Olkowski, L. C. Weir, G. F. Smith, Bioorg. Med. Chem. Lett. 1996, 6, 2387. http://www.sciencedirect.com/science/article/pii/0960894X96004428 </ref></div></td></tr> <tr><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"></td><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"></td></tr> </table>

Sean Swale http://52.214.119.220/wiki/index.php?title=Sean_Swale/Human_Thrombin_Inhibitor&diff=1609292&oldid=prev Sean Swale at 20:15, 16 November 2012 2012-11-16T20:15:50Z

<p></p> <table style="background-color: white; color:black;"> <col class='diff-marker' /> <col class='diff-content' /> <col class='diff-marker' /> <col class='diff-content' /> <tr> <td colspan='2' style="background-color: white; color:black;">←Older revision</td> <td colspan='2' style="background-color: white; color:black;">Revision as of 20:15, 16 November 2012</td> </tr> <tr><td colspan="2" class="diff-lineno">Line 8:</td> <td colspan="2" class="diff-lineno">Line 8:</td></tr> <tr><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"><div>===Phe-Pro-p-amidinobenzylamine===</div></td><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"><div>===Phe-Pro-p-amidinobenzylamine===</div></td></tr> <tr><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"><div>An early experiment to find a better thrombin inhibitor yielded a structure that was able to bond to the P1 and P2 sites of Thrombin effectively. In 1996 Lilly research laboratories created D-Phe-Pro-p-amidinobenzylamine by making improvements on the previous structure D-Phe-Pro-Agmatine. The new compound they created bonded to thrombin 130x more than it did to trypsin (also a serine protease), and it was highly selective of thrombin over fibrinolytic enzymes which break down fibrin clots. The inhibitor bound with Thrombin at rates 26,000x greater than with plasmin,<ref> http://voices.yahoo.com/what-fibrinolytic-enzymes-6186058.html?cat=68</ref>, 170,000x greater than with t-Pa, and 400,000x greater than with urokinase. </div></td><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"><div>An early experiment to find a better thrombin inhibitor yielded a structure that was able to bond to the P1 and P2 sites of Thrombin effectively. In 1996 Lilly research laboratories created D-Phe-Pro-p-amidinobenzylamine by making improvements on the previous structure D-Phe-Pro-Agmatine. The new compound they created bonded to thrombin 130x more than it did to trypsin (also a serine protease), and it was highly selective of thrombin over fibrinolytic enzymes which break down fibrin clots. The inhibitor bound with Thrombin at rates 26,000x greater than with plasmin,<ref> http://voices.yahoo.com/what-fibrinolytic-enzymes-6186058.html?cat=68</ref>, 170,000x greater than with t-Pa, and 400,000x greater than with urokinase. </div></td></tr> <tr><td class='diff-marker'>-</td><td style="background: #ffa; color:black; font-size: smaller;"><div>[[Image:1996 inhibitor rates.png|left|<del style="color: red; font-weight: bold; text-decoration: none;">100px</del>|frame|Inhibitor 12 is the identical P1 and P2 sites of Inhibitor 65.(1996)<ref> M. R. Wiley, N. Y. Chirgadze, D. K. Clawson, T. J. Craft, D. S. GiffordMoore, N. D. Jones, J. L. Olkowski, L. C. Weir, G. F. Smith, Bioorg. Med. Chem. Lett. 1996, 6, 2387. http://www.sciencedirect.com/science/article/pii/0960894X96004428 </ref>]]</div></td><td class='diff-marker'>+</td><td style="background: #cfc; color:black; font-size: smaller;"><div>[[Image:1996 inhibitor rates.png|left|<ins style="color: red; font-weight: bold; text-decoration: none;">100</ins>|frame|Inhibitor 12 is the identical P1 and P2 sites of Inhibitor 65.(1996)<ref> M. R. Wiley, N. Y. Chirgadze, D. K. Clawson, T. J. Craft, D. S. GiffordMoore, N. D. Jones, J. L. Olkowski, L. C. Weir, G. F. Smith, Bioorg. Med. Chem. Lett. 1996, 6, 2387. http://www.sciencedirect.com/science/article/pii/0960894X96004428 </ref>]]</div></td></tr> <tr><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"><div>Its selectivity was gained by binding its nitrogens on the benzamidine <scene name='Sean_Swale/Human_Thrombin_Inhibitor/P1_residue/1'>group</scene> by hydrogen bonding to Asp 189, and by fitting its benzamidine benzene into a hydrophobic pocket with Ser 214-Glu 217 and Asp 189-Glu 192 on the other side. The <scene name='Sean_Swale/Human_Thrombin_Inhibitor/P2_proline/1'>proline</scene> residue is in another hydrophobic pocket made up of His 57, Tyr 60A, Leu 99, and Trp 60D. The rest of this structure is unimportant on review of inhibitor 65 because only the amidinobenzylamine which occupies R1 and the proline which occupies the R2 sit are the same residues on inhibitor 65.<ref> M. R. Wiley, N. Y. Chirgadze, D. K. Clawson, T. J. Craft, D. S. GiffordMoore, N. D. Jones, J. L. Olkowski, L. C. Weir, G. F. Smith, Bioorg. Med. Chem. Lett. 1996, 6, 2387. http://www.sciencedirect.com/science/article/pii/0960894X96004428 </ref></div></td><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"><div>Its selectivity was gained by binding its nitrogens on the benzamidine <scene name='Sean_Swale/Human_Thrombin_Inhibitor/P1_residue/1'>group</scene> by hydrogen bonding to Asp 189, and by fitting its benzamidine benzene into a hydrophobic pocket with Ser 214-Glu 217 and Asp 189-Glu 192 on the other side. The <scene name='Sean_Swale/Human_Thrombin_Inhibitor/P2_proline/1'>proline</scene> residue is in another hydrophobic pocket made up of His 57, Tyr 60A, Leu 99, and Trp 60D. The rest of this structure is unimportant on review of inhibitor 65 because only the amidinobenzylamine which occupies R1 and the proline which occupies the R2 sit are the same residues on inhibitor 65.<ref> M. R. Wiley, N. Y. Chirgadze, D. K. Clawson, T. J. Craft, D. S. GiffordMoore, N. D. Jones, J. L. Olkowski, L. C. Weir, G. F. Smith, Bioorg. Med. Chem. Lett. 1996, 6, 2387. http://www.sciencedirect.com/science/article/pii/0960894X96004428 </ref></div></td></tr> <tr><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"></td><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"></td></tr> </table>

Sean Swale http://52.214.119.220/wiki/index.php?title=Sean_Swale/Human_Thrombin_Inhibitor&diff=1609291&oldid=prev Sean Swale at 20:12, 16 November 2012 2012-11-16T20:12:20Z

<p></p> <table style="background-color: white; color:black;"> <col class='diff-marker' /> <col class='diff-content' /> <col class='diff-marker' /> <col class='diff-content' /> <tr> <td colspan='2' style="background-color: white; color:black;">←Older revision</td> <td colspan='2' style="background-color: white; color:black;">Revision as of 20:12, 16 November 2012</td> </tr> <tr><td colspan="2" class="diff-lineno">Line 8:</td> <td colspan="2" class="diff-lineno">Line 8:</td></tr> <tr><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"><div>===Phe-Pro-p-amidinobenzylamine===</div></td><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"><div>===Phe-Pro-p-amidinobenzylamine===</div></td></tr> <tr><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"><div>An early experiment to find a better thrombin inhibitor yielded a structure that was able to bond to the P1 and P2 sites of Thrombin effectively. In 1996 Lilly research laboratories created D-Phe-Pro-p-amidinobenzylamine by making improvements on the previous structure D-Phe-Pro-Agmatine. The new compound they created bonded to thrombin 130x more than it did to trypsin (also a serine protease), and it was highly selective of thrombin over fibrinolytic enzymes which break down fibrin clots. The inhibitor bound with Thrombin at rates 26,000x greater than with plasmin,<ref> http://voices.yahoo.com/what-fibrinolytic-enzymes-6186058.html?cat=68</ref>, 170,000x greater than with t-Pa, and 400,000x greater than with urokinase. </div></td><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"><div>An early experiment to find a better thrombin inhibitor yielded a structure that was able to bond to the P1 and P2 sites of Thrombin effectively. In 1996 Lilly research laboratories created D-Phe-Pro-p-amidinobenzylamine by making improvements on the previous structure D-Phe-Pro-Agmatine. The new compound they created bonded to thrombin 130x more than it did to trypsin (also a serine protease), and it was highly selective of thrombin over fibrinolytic enzymes which break down fibrin clots. The inhibitor bound with Thrombin at rates 26,000x greater than with plasmin,<ref> http://voices.yahoo.com/what-fibrinolytic-enzymes-6186058.html?cat=68</ref>, 170,000x greater than with t-Pa, and 400,000x greater than with urokinase. </div></td></tr> <tr><td class='diff-marker'>-</td><td style="background: #ffa; color:black; font-size: smaller;"><div>[[Image:1996 inhibitor rates.png|<del style="color: red; font-weight: bold; text-decoration: none;">center</del>|100px|frame|Inhibitor 12 is the identical P1 and P2 sites of Inhibitor 65.(1996)<ref> M. R. Wiley, N. Y. Chirgadze, D. K. Clawson, T. J. Craft, D. S. GiffordMoore, N. D. Jones, J. L. Olkowski, L. C. Weir, G. F. Smith, Bioorg. Med. Chem. Lett. 1996, 6, 2387. http://www.sciencedirect.com/science/article/pii/0960894X96004428 </ref>]]</div></td><td class='diff-marker'>+</td><td style="background: #cfc; color:black; font-size: smaller;"><div>[[Image:1996 inhibitor rates.png|<ins style="color: red; font-weight: bold; text-decoration: none;">left</ins>|100px|frame|Inhibitor 12 is the identical P1 and P2 sites of Inhibitor 65.(1996)<ref> M. R. Wiley, N. Y. Chirgadze, D. K. Clawson, T. J. Craft, D. S. GiffordMoore, N. D. Jones, J. L. Olkowski, L. C. Weir, G. F. Smith, Bioorg. Med. Chem. Lett. 1996, 6, 2387. http://www.sciencedirect.com/science/article/pii/0960894X96004428 </ref>]]</div></td></tr> <tr><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"><div>Its selectivity was gained by binding its nitrogens on the benzamidine <scene name='Sean_Swale/Human_Thrombin_Inhibitor/P1_residue/1'>group</scene> by hydrogen bonding to Asp 189, and by fitting its benzamidine benzene into a hydrophobic pocket with Ser 214-Glu 217 and Asp 189-Glu 192 on the other side. The <scene name='Sean_Swale/Human_Thrombin_Inhibitor/P2_proline/1'>proline</scene> residue is in another hydrophobic pocket made up of His 57, Tyr 60A, Leu 99, and Trp 60D. The rest of this structure is unimportant on review of inhibitor 65 because only the amidinobenzylamine which occupies R1 and the proline which occupies the R2 sit are the same residues on inhibitor 65.<ref> M. R. Wiley, N. Y. Chirgadze, D. K. Clawson, T. J. Craft, D. S. GiffordMoore, N. D. Jones, J. L. Olkowski, L. C. Weir, G. F. Smith, Bioorg. Med. Chem. Lett. 1996, 6, 2387. http://www.sciencedirect.com/science/article/pii/0960894X96004428 </ref></div></td><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"><div>Its selectivity was gained by binding its nitrogens on the benzamidine <scene name='Sean_Swale/Human_Thrombin_Inhibitor/P1_residue/1'>group</scene> by hydrogen bonding to Asp 189, and by fitting its benzamidine benzene into a hydrophobic pocket with Ser 214-Glu 217 and Asp 189-Glu 192 on the other side. The <scene name='Sean_Swale/Human_Thrombin_Inhibitor/P2_proline/1'>proline</scene> residue is in another hydrophobic pocket made up of His 57, Tyr 60A, Leu 99, and Trp 60D. The rest of this structure is unimportant on review of inhibitor 65 because only the amidinobenzylamine which occupies R1 and the proline which occupies the R2 sit are the same residues on inhibitor 65.<ref> M. R. Wiley, N. Y. Chirgadze, D. K. Clawson, T. J. Craft, D. S. GiffordMoore, N. D. Jones, J. L. Olkowski, L. C. Weir, G. F. Smith, Bioorg. Med. Chem. Lett. 1996, 6, 2387. http://www.sciencedirect.com/science/article/pii/0960894X96004428 </ref></div></td></tr> <tr><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"></td><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"></td></tr> <tr><td colspan="2" class="diff-lineno">Line 16:</td> <td colspan="2" class="diff-lineno">Line 16:</td></tr> <tr><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"><div>[[Image:Inhibitor 65.png|center|200px|frame|<ref> DOI: 10.1002/cmdc.201200292</ref> ]]</div></td><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"><div>[[Image:Inhibitor 65.png|center|200px|frame|<ref> DOI: 10.1002/cmdc.201200292</ref> ]]</div></td></tr> <tr><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"><div>Inhibitor 65 additionally has a <scene name='Sean_Swale/Human_Thrombin_Inhibitor/P4/1'>P4</scene> sulfonyl group with a methoxy group at the end of the residue. The residue sits in a hydrophobic <scene name='Sean_Swale/Human_Thrombin_Inhibitor/P4_binding_pocket/1'>pocket</scene>. It sits in tight VanderWaals structure with the surrounding residues Leu 99, Tyr 60A, Arg 97, Glu 97, and Asn 98.The <scene name='Sean_Swale/Human_Thrombin_Inhibitor/P4_sulfonyl/1'>sulfonyl</scene> group holds its own VanderWaal forces. Additionally, the <scene name='Sean_Swale/Human_Thrombin_Inhibitor/P4_chlorine/1'>chlorine</scene> points to the carbonyl oxygen of Asn 98 and there is a weak Cl-π bond with Trp 215. For the P3 <scene name='Sean_Swale/Human_Thrombin_Inhibitor/P3_binding_site/6'>residue</scene>, there the backbone of asparagine forms and anti parallel beta sheet with Gly 216. The alkylated asparagine’s NH binds to a water molecule which then connects to Glu 192, and the hydrogens of Gly 219 and Gly 216.</div></td><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"><div>Inhibitor 65 additionally has a <scene name='Sean_Swale/Human_Thrombin_Inhibitor/P4/1'>P4</scene> sulfonyl group with a methoxy group at the end of the residue. The residue sits in a hydrophobic <scene name='Sean_Swale/Human_Thrombin_Inhibitor/P4_binding_pocket/1'>pocket</scene>. It sits in tight VanderWaals structure with the surrounding residues Leu 99, Tyr 60A, Arg 97, Glu 97, and Asn 98.The <scene name='Sean_Swale/Human_Thrombin_Inhibitor/P4_sulfonyl/1'>sulfonyl</scene> group holds its own VanderWaal forces. Additionally, the <scene name='Sean_Swale/Human_Thrombin_Inhibitor/P4_chlorine/1'>chlorine</scene> points to the carbonyl oxygen of Asn 98 and there is a weak Cl-π bond with Trp 215. For the P3 <scene name='Sean_Swale/Human_Thrombin_Inhibitor/P3_binding_site/6'>residue</scene>, there the backbone of asparagine forms and anti parallel beta sheet with Gly 216. The alkylated asparagine’s NH binds to a water molecule which then connects to Glu 192, and the hydrogens of Gly 219 and Gly 216.</div></td></tr> <tr><td class='diff-marker'>-</td><td style="background: #ffa; color:black; font-size: smaller;"><div>[[Image:Thrombin1.gif|left|frame|<del style="color: red; font-weight: bold; text-decoration: none;">300px</del>|a) Stereo view of the complete inhibitor structure provided with its electron density in the active site of thrombin. Thrombin is shown with its solvent- accessible surface. b) The P4 sulfonyl residue is located in the aryl binding pocket. The chlorine atom points to the carbonyl oxygen of Asn 98 and accommodates a position above the indole moiety of Trp 215. The methoxy group perfectly fills the upper niche of the S3/4 pocket. c) The P3 side chain is directed into the solvent, where its amide NH binds via a bridging water molecule to Glu 192, Gly 216 and Gly 219.<ref> DOI: 10.1002/cmdc.201200292</ref> ]]</div></td><td class='diff-marker'>+</td><td style="background: #cfc; color:black; font-size: smaller;"><div>[[Image:Thrombin1.gif|left|frame|<ins style="color: red; font-weight: bold; text-decoration: none;">200px</ins>|a) Stereo view of the complete inhibitor structure provided with its electron density in the active site of thrombin. Thrombin is shown with its solvent- accessible surface. b) The P4 sulfonyl residue is located in the aryl binding pocket. The chlorine atom points to the carbonyl oxygen of Asn 98 and accommodates a position above the indole moiety of Trp 215. The methoxy group perfectly fills the upper niche of the S3/4 pocket. c) The P3 side chain is directed into the solvent, where its amide NH binds via a bridging water molecule to Glu 192, Gly 216 and Gly 219.<ref> DOI: 10.1002/cmdc.201200292</ref> ]]</div></td></tr> <tr><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"></td><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"></td></tr> <tr><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"><div></StructureSection></div></td><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"><div></StructureSection></div></td></tr> </table>

Sean Swale