2e1w: Difference between revisions

[[Image:2e1w.gif|left|200px]]<br /><applet load="2e1w" size="450" color="white" frame="true" align="right" spinBox="true"  

We disclose optimization efforts based on the novel non-nucleoside, adenosine deaminase (ADA) inhibitor, 4 (K(i) = 680 nM). Structure-based, drug design utilizing the crystal structure of the 4/ADA complex led to, discovery of 5 (K(i) = 11 nM, BA = 30% in rats). Furthermore, from, metabolic considerations, we discovered two inhibitors with improved oral, bioavailability [6 (K(i) = 13 nM, BA = 44%) and 7 (K(i) = 9.8 nM, BA =, 42%)]. 6 demonstrated in vivo efficacy in models of inflammation and, lymphoma.

2E1W is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Bos_taurus Bos taurus] with ZN and FR6 as [http://en.wikipedia.org/wiki/ligands ligands]. This structure superseeds the now removed PDB entry 1V78. Active as [http://en.wikipedia.org/wiki/Adenosine_deaminase Adenosine deaminase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.5.4.4 3.5.4.4] Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=2E1W OCA].  

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