INDUCIBLE NITRIC OXIDE SYNTHASE INHIBITOR COMPLEX DATA COLLECTION

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We have to collect seven high resolution data sets from flash frozen crystals of the oxygenase domain of inducible nitric oxide synthase (iNOS) inhibitor complexes at -180 C using monochromatic radiation around 1.0 E at beam line 7-1 or 9-1. Synchrotron radiation has been and still is needed due to the weak diffraction of the iNOS crystals, which only diffract to 3.5 E using a rotating anode. These structures have helped us develop selective proprietary inhibitors of human iNOS. The structural information we have gained from the high resolution structures has and will significantly enhance our ability to understand binding of these inhibitors to the iNOS and aid in the design of future iNOS inhibitors. We have been able to increase the potency of one template by 100 fold, and we now have a better understanding of the selectivity of our compounds between iNOS, nNOS and ecNOS.