Development of molecules stimulating the activity of KLK3 – an update
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Hannu Koistinen
, Erik Wallén
Abstract
Kallikrein-related peptidase-3 (KLK3, known also as prostate-specific antigen, PSA) is highly expressed in the prostate. KLK3 possess antiangiogenic activity, which we have found to be related to its proteolytic activity. Thus, it may be possible to slow down the growth of prostatic tumors by enhancing this activity. We have developed peptides that enhance the proteolytic activity of KLK3. As these peptides are degraded in circulation and rapidly excreted, we have started to modify them and have succeeded in creating bioactive and more stable pseudopeptides. We have also identified small molecules stimulating the activity of KLK3, especially in synergy with peptides.
Acknowledgments
Our original studies reviewed in this paper have been supported by grants from the Helsinki University Central Hospital, the Finnish Cancer Foundation, the Academy of Finland, Sigrid Jusélius Foundation, Graduate School of Organic Chemistry and Chemical Biology, the Research Funds of the University of Helsinki, Finska Läkaresällskapet, Finnish Funding Agency for Technology and Innovation, Magnus Ehrnrooth Foundation, the Swedish Research Council and Biomedicum Helsinki Foundation.
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©2016 Walter de Gruyter GmbH, Berlin/Boston
Artikel in diesem Heft
- Frontmatter
- Guest Editorial
- Highlight: remodelling the KLK landscape down under
- HIGHLIGHT: 6TH INTERNATIONAL SYMPOSIUM ON KALLIKREINS AND KALLIKREIN-RELATED PEPTIDASES
- Kallikrein(K1)-kinin-kininase (ACE) and end-organ damage in ischemia and diabetes: therapeutic implications
- Mechanistic insight from murine models of Netherton syndrome
- Development of molecules stimulating the activity of KLK3 – an update
- Exploring the active site binding specificity of kallikrein-related peptidase 5 (KLK5) guides the design of new peptide substrates and inhibitors
- Structural basis for the Zn2+ inhibition of the zymogen-like kallikrein-related peptidase 10
- Clinical relevance of kallikrein-related peptidase 6 (KLK6) and 8 (KLK8) mRNA expression in advanced serous ovarian cancer
- Kallikrein-related peptidase 6 exacerbates disease in an autoimmune model of multiple sclerosis
- A viable mouse model for Netherton syndrome based on mosaic inactivation of the Spink5 gene
- Therapeutic modulation of tissue kallikrein expression
- In vitro evidence that KLK14 regulates the components of the HGF/Met axis, pro-HGF and HGF-activator inhibitor 1A and 1B
- A computational analysis of the genetic and transcript diversity at the kallikrein locus
- Reviews
- Lymphocyte signaling and activation by the CARMA1-BCL10-MALT1 signalosome
- The power, pitfalls and potential of the nanodisc system for NMR-based studies
- Research Articles/Short Communications
- Cell Biology and Signaling
- Synergistic induction of cardiomyocyte differentiation from human bone marrow mesenchymal stem cells by interleukin 1β and 5-azacytidine
Artikel in diesem Heft
- Frontmatter
- Guest Editorial
- Highlight: remodelling the KLK landscape down under
- HIGHLIGHT: 6TH INTERNATIONAL SYMPOSIUM ON KALLIKREINS AND KALLIKREIN-RELATED PEPTIDASES
- Kallikrein(K1)-kinin-kininase (ACE) and end-organ damage in ischemia and diabetes: therapeutic implications
- Mechanistic insight from murine models of Netherton syndrome
- Development of molecules stimulating the activity of KLK3 – an update
- Exploring the active site binding specificity of kallikrein-related peptidase 5 (KLK5) guides the design of new peptide substrates and inhibitors
- Structural basis for the Zn2+ inhibition of the zymogen-like kallikrein-related peptidase 10
- Clinical relevance of kallikrein-related peptidase 6 (KLK6) and 8 (KLK8) mRNA expression in advanced serous ovarian cancer
- Kallikrein-related peptidase 6 exacerbates disease in an autoimmune model of multiple sclerosis
- A viable mouse model for Netherton syndrome based on mosaic inactivation of the Spink5 gene
- Therapeutic modulation of tissue kallikrein expression
- In vitro evidence that KLK14 regulates the components of the HGF/Met axis, pro-HGF and HGF-activator inhibitor 1A and 1B
- A computational analysis of the genetic and transcript diversity at the kallikrein locus
- Reviews
- Lymphocyte signaling and activation by the CARMA1-BCL10-MALT1 signalosome
- The power, pitfalls and potential of the nanodisc system for NMR-based studies
- Research Articles/Short Communications
- Cell Biology and Signaling
- Synergistic induction of cardiomyocyte differentiation from human bone marrow mesenchymal stem cells by interleukin 1β and 5-azacytidine