Substrate-guided design of a potent and selective kallikrein-related peptidase inhibitor for kallikrein 4

Swedberg, Joakim E., Nigon, Laura V., Reid, Janet C., de Veer, Simon J., Walpole, Carina M., Stephens, Carson R., Walsh, Terry P., Takayama, Thomas K., Hooper, John D., Clements, Judith A., Buckle, Ashley M. and Harris, Jonathan M. (2009) Substrate-guided design of a potent and selective kallikrein-related peptidase inhibitor for kallikrein 4. Chemistry and Biology, 16 6: 633-643. doi:10.1016/j.chembiol.2009.05.008


Author Swedberg, Joakim E.
Nigon, Laura V.
Reid, Janet C.
de Veer, Simon J.
Walpole, Carina M.
Stephens, Carson R.
Walsh, Terry P.
Takayama, Thomas K.
Hooper, John D.
Clements, Judith A.
Buckle, Ashley M.
Harris, Jonathan M.
Title Substrate-guided design of a potent and selective kallikrein-related peptidase inhibitor for kallikrein 4
Journal name Chemistry and Biology   Check publisher's open access policy
ISSN 1074-5521
1879-1301
Publication date 2009-06-26
Sub-type Article (original research)
DOI 10.1016/j.chembiol.2009.05.008
Volume 16
Issue 6
Start page 633
End page 643
Total pages 11
Place of publication Cambridge, MA, U.S.A.
Publisher Cell Press
Language eng
Formatted abstract
Human 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.
Keyword CHEMBIO
Proteins
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: Institute for Molecular Bioscience - Publications
 
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Created: Mon, 05 Sep 2011, 14:59:58 EST by Susan Allen on behalf of Institute for Molecular Bioscience