A rapid method to identify exo-protease inhibitors

Abstract A new approach to the evaluation of exo -protease inhibitor candidates is presented. The application of new water-soluble substrates that release organic-soluble fluorescent groups upon proteolytic cleavage allows amplification of the assay signal via concentration of the cleavage product. A combinatorial library of disubstituted xanthenes designed to resemble a known inhibitor was screened and a new HLE inhibitor (K i = 79 μM) was identified.