Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
10766964 | Biochemical and Biophysical Research Communications | 2007 | 7 Pages |
Abstract
In this report, we describe a novel phage display strategy for the identification of dedicated protease inhibiting peptides, based on degradation-aided enrichment of protease resistant phages. Phages were directly incubated with a range of phage-degrading proteases, after which non-degraded phages were used for the next selection round. For proteinase-K we identified after only four selection rounds a peptide (VLIMPVLLGIPLLC) that inhibits proteinase-K activity with an inhibition constant of 4 μM. In analogy, we identified a peptide capable of inhibiting substrate degradation by cathepsin-S (VWNCERITISRLIN), which showed functional inhibition of cathepsin-S induced sprouting of endothelial cells. We envision that the pursued strategy of degradation-aided selection of protease inhibitors (DASPI) represents an effective approach in the design of new protease inhibitors but also of new strategies to render gene and drug vectors protease resistant.
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Authors
Lukas J.A.C. Hawinkels, Sabine M.W. van Rossenberg, Eveline S.M. de Jonge-Muller, Tom J.M. Molenaar, Chantal C.M. Appeldoorn, Theo J.C. van Berkel, Cornelis F.M. Sier, Erik A.L. Biessen,