2viq: Difference between revisions

Fragment-based lead discovery has been applied to urokinase-type, plasminogen activator (uPA). The ( R)-enantiomer of the orally active drug, mexiletine 5 (a fragment hit from X-ray crystallographic screening) was, the chemical starting point. Structure-aided design led to elaborated, inhibitors that retained the key interactions of ( R)- 5 while gaining, extra potency by simultaneously occupying neighboring regions of the, active site. Subsequent optimization led to 15, a potent, selective, and, orally bioavailable inhibitor of uPA.

2VIQ 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=ACT:'>ACT</scene> and <scene name='pdbligand=D55:'>D55</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/U-plasminogen_activator U-plasminogen activator], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.21.73 3.4.21.73] Known structural/functional Sites: <scene name='pdbsite=AC1:Act Binding Site For Chain A'>AC1</scene> and <scene name='pdbsite=AC2:D55 Binding Site For Chain A'>AC2</scene>. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2VIQ OCA].  

[[Category: Cowan, S.R.]]

[[Category: Matthews, J.E.]]

[[Category: Wallis, N.G.]]

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