Discovery of Thrombin Inhibitor Fragments from Chemical Microarray Screening

Surface plasmon resonance imaging, a low affinity screening method, allows the highly parallel detection of small molecules binding to a target protein. The screening of a fragment based compound library immobilized on chemical microarrays resulted in the discovery of binding fragments for the serine protease thrombin. Functional assays confirmed enzymatic inhibition of microarray hits and crystallography established the binding mode of a non-basic S1 motif providing a starting point for medicinal chemistry.