1d8f: Difference between revisions

[[Image:1d8f.gif|left|200px]]<br /><applet load="1d8f" size="350" color="white" frame="true" align="right" spinBox="true"  

A new generation of cyclic matrix metalloproteinase (MMP) inhibitors derived from dl-piperazinecarboxylic acid has been described. The design involves: incorporation of hydroxamic acid as the bidentate chelating agent for catalytic Zn(2+), placement of a sulfonamide group at the 1N-position of the piperazine ring to fill the S1' pocket of the enzyme, and finally attachment of diverse functional groups at the 4N-position to optimize potency and peroral absorption. A unique combination of all three elements produced inhibitor 20 with high affinity for MMPs 1, 3, 9, and 13 (24, 18, 1.9, and 1.3 nM, respectively). X-ray crystallography data obtained for MMP-3 cocrystallized with 20 gave detailed information on key binding interactions defining an overall scaffold geometry for piperazine-based MMP inhibitors.

1D8F is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=ZN:'>ZN</scene>, <scene name='pdbligand=CA:'>CA</scene> and <scene name='pdbligand=SPI:'>SPI</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Stromelysin_1 Stromelysin 1], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.24.17 3.4.24.17] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1D8F OCA].  

[[Category: Almstead, N G.]]

[[Category: Anastasio, M V.]]

[[Category: Chen, L Y.]]

[[Category: Cheng, M Y.]]

[[Category: McPhail, S J.]]

[[Category: Natchus, M G.]]

[[Category: Snider, C E.]]

[[Category: Taiwo, Y O.]]

''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 12:14:05 2008''