Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
1391467 | Chemistry & Biology | 2009 | 11 Pages |
Abstract
SummaryHuman kallikrein-related peptidase 4 (KLK4/prostase), a trypsin-like serine protease, is a potential target for prostate cancer treatment because of its proteolytic ability to activate many tumorigenic and metastatic pathways including the protease activated receptors (PARs). Currently there are no KLK4-specific small-molecule inhibitors available for therapeutic development. Here we re-engineer the naturally occurring sunflower trypsin inhibitor to selectively block the proteolytic activity of KLK4 and prevent stimulation of PAR activity in a cell-based system. The re-engineered inhibitor was designed using a combination of molecular modeling and sparse matrix substrate screening.
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Authors
Joakim E. Swedberg, Laura V. Nigon, Janet C. Reid, Simon J. de Veer, Carina M. Walpole, Carson R. Stephens, Terry P. Walsh, Thomas K. Takayama, John D. Hooper, Judith A. Clements, Ashley M. Buckle, Jonathan M. Harris,