1eau
From Proteopedia
| Line 1: | Line 1: | ||
| - | [[Image:1eau.jpg|left|200px]] | + | [[Image:1eau.jpg|left|200px]] |
| - | + | ||
| - | '''NONPEPTIDIC INHIBITORS OF HUMAN LEUKOCYTE ELASTASE. 6. DESIGN OF A POTENT, INTRATRACHEALLY ACTIVE, PYRIDONE-BASED TRIFLUOROMETHYL KETONE''' | + | {{Structure |
| + | |PDB= 1eau |SIZE=350|CAPTION= <scene name='initialview01'>1eau</scene>, resolution 2.0Å | ||
| + | |SITE= | ||
| + | |LIGAND= <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene> and <scene name='pdbligand=BDK:2-[5-AMINO-6-OXO-2-(2-THIENYL)-1,6-DIHYDROPYRIMIDIN-1-YL)-N-[3,3-DIFLUORO -1-ISOPROPYL-2-OXO-3-(N-(2-MORPHOLINO ETHYL)CARBAMOYL]PROPYL]ACETAMIDE'>BDK</scene> | ||
| + | |ACTIVITY= [http://en.wikipedia.org/wiki/Pancreatic_elastase Pancreatic elastase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.21.36 3.4.21.36] | ||
| + | |GENE= | ||
| + | }} | ||
| + | |||
| + | '''NONPEPTIDIC INHIBITORS OF HUMAN LEUKOCYTE ELASTASE. 6. DESIGN OF A POTENT, INTRATRACHEALLY ACTIVE, PYRIDONE-BASED TRIFLUOROMETHYL KETONE''' | ||
| + | |||
==Overview== | ==Overview== | ||
| Line 7: | Line 16: | ||
==About this Structure== | ==About this Structure== | ||
| - | 1EAU is a [ | + | 1EAU is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Sus_scrofa Sus scrofa]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1EAU OCA]. |
==Reference== | ==Reference== | ||
| - | Nonpeptidic inhibitors of human leukocyte elastase. 6. Design of a potent, intratracheally active, pyridone-based trifluoromethyl ketone., Bernstein PR, Gomes BC, Kosmider BJ, Vacek EP, Williams JC, J Med Chem. 1995 Jan 6;38(1):212-5. PMID:[http:// | + | Nonpeptidic inhibitors of human leukocyte elastase. 6. Design of a potent, intratracheally active, pyridone-based trifluoromethyl ketone., Bernstein PR, Gomes BC, Kosmider BJ, Vacek EP, Williams JC, J Med Chem. 1995 Jan 6;38(1):212-5. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/7837235 7837235] |
[[Category: Pancreatic elastase]] | [[Category: Pancreatic elastase]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| Line 20: | Line 29: | ||
[[Category: hydrolase (serine protease)]] | [[Category: hydrolase (serine protease)]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 10:52:49 2008'' |
Revision as of 08:52, 20 March 2008
| |||||||
| , resolution 2.0Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | , and | ||||||
| Activity: | Pancreatic elastase, with EC number 3.4.21.36 | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
NONPEPTIDIC INHIBITORS OF HUMAN LEUKOCYTE ELASTASE. 6. DESIGN OF A POTENT, INTRATRACHEALLY ACTIVE, PYRIDONE-BASED TRIFLUOROMETHYL KETONE
Overview
Further modification of the 3-amino substituent in a trifluoromethyl ketone-based series of 3-amino-6-phenylpyridin-2-ones that had been optimized for oral activity led to analogs that were potent intratracheal inhibitors in a model of HLE-induced lung damage in the hamster. The best 3-amino substituent for intratracheal activity is [4-[N-[(4-chlorophenyl)sulfonyl]-carbamoyl]phenyl]sulfonyl. At a 30 min prechallenge interval, compound 9, which incorporates this substituent, had an ED50 of approximately 2 nmol/animal and, qualitatively, afforded a very similar dose-response relationship to that found with a peptidic trifluoromethyl ketone inhibitor, ICI 200,355.
About this Structure
1EAU is a Single protein structure of sequence from Sus scrofa. Full crystallographic information is available from OCA.
Reference
Nonpeptidic inhibitors of human leukocyte elastase. 6. Design of a potent, intratracheally active, pyridone-based trifluoromethyl ketone., Bernstein PR, Gomes BC, Kosmider BJ, Vacek EP, Williams JC, J Med Chem. 1995 Jan 6;38(1):212-5. PMID:7837235
Page seeded by OCA on Thu Mar 20 10:52:49 2008
