rdf:type |
|
lifeskim:mentions |
|
pubmed:issue |
6
|
pubmed:dateCreated |
2009-6-24
|
pubmed:abstractText |
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.
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pubmed:language |
eng
|
pubmed:journal |
|
pubmed:citationSubset |
IM
|
pubmed:chemical |
|
pubmed:status |
MEDLINE
|
pubmed:month |
Jun
|
pubmed:issn |
1879-1301
|
pubmed:author |
pubmed-author:BuckleAshley MAM,
pubmed-author:ClementsJudith AJA,
pubmed-author:HarrisJonathan MJM,
pubmed-author:HooperJohn DJD,
pubmed-author:NigonLaura VLV,
pubmed-author:ReidJanet CJC,
pubmed-author:StephensCarson RCR,
pubmed-author:SwedbergJoakim EJE,
pubmed-author:TakayamaThomas KTK,
pubmed-author:WalpoleCarina MCM,
pubmed-author:WalshTerry PTP,
pubmed-author:de VeerSimon JSJ
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pubmed:issnType |
Electronic
|
pubmed:day |
26
|
pubmed:volume |
16
|
pubmed:owner |
NLM
|
pubmed:authorsComplete |
Y
|
pubmed:pagination |
633-43
|
pubmed:meshHeading |
pubmed-meshheading:19549601-Animals,
pubmed-meshheading:19549601-Catalytic Domain,
pubmed-meshheading:19549601-Cell Line, Tumor,
pubmed-meshheading:19549601-Computer Simulation,
pubmed-meshheading:19549601-Drug Design,
pubmed-meshheading:19549601-Humans,
pubmed-meshheading:19549601-Kallikreins,
pubmed-meshheading:19549601-Kinetics,
pubmed-meshheading:19549601-Male,
pubmed-meshheading:19549601-Mice,
pubmed-meshheading:19549601-Peptide Library,
pubmed-meshheading:19549601-Peptides,
pubmed-meshheading:19549601-Prostatic Neoplasms,
pubmed-meshheading:19549601-Protein Conformation,
pubmed-meshheading:19549601-Receptors, Proteinase-Activated,
pubmed-meshheading:19549601-Serine Proteinase Inhibitors,
pubmed-meshheading:19549601-Substrate Specificity
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pubmed:year |
2009
|
pubmed:articleTitle |
Substrate-guided design of a potent and selective kallikrein-related peptidase inhibitor for kallikrein 4.
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pubmed:affiliation |
Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Queensland 4059, Australia.
|
pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
|