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Biological Chemistry

Editor-in-Chief: Brüne, Bernhard

Editorial Board Member: Buchner, Johannes / Lei, Ming / Ludwig, Stephan / Sies, Helmut / Turk, Boris / Wittinghofer, Alfred


SCImago Journal Rank (SJR) 2015: 1.607
Source Normalized Impact per Paper (SNIP) 2015: 0.751
Impact per Publication (IPP) 2015: 2.609

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1437-4315
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Development of peptides specifically modulating the activity of KLK2 and KLK3

Hannu Koistinen1 / Ale Närvänen2 / Miikka Pakkala3 / Can Hekim4 / Johanna M. Mattsson5 / Lei Zhu6 / Pirjo Laakkonen7 / Ulf-Håkan Stenman8

1Department of Clinical Chemistry, Biomedicum Helsinki, University of Helsinki and Helsinki University Central Hospital, 00014 Helsinki, Finland

2Department of Biosciences and AIV Institute, University of Kuopio, 70211 Kuopio, Finland

3Department of Biosciences and AIV Institute, University of Kuopio, 70211 Kuopio, Finland

4Department of Clinical Chemistry, Biomedicum Helsinki, University of Helsinki and Helsinki University Central Hospital, 00014 Helsinki, Finland

5Department of Clinical Chemistry, Biomedicum Helsinki, University of Helsinki and Helsinki University Central Hospital, 00014 Helsinki, Finland

6Department of Clinical Chemistry, Biomedicum Helsinki, University of Helsinki and Helsinki University Central Hospital, 00014 Helsinki, Finland

7Molecular Cancer Biology Research Program and Institute of Biomedicine, Biomedicum Helsinki, University of Helsinki, 00014 Helsinki, Finland

8Department of Clinical Chemistry, Biomedicum Helsinki, University of Helsinki and Helsinki University Central Hospital, 00014 Helsinki, Finland

Corresponding author

Citation Information: Biological Chemistry. Volume 389, Issue 6, Pages 633–642, ISSN (Online) 14374315, ISSN (Print) 1431-6730, DOI: 10.1515/BC.2008.076, May 2008

Publication History

Published Online:
2008-05-15

Abstract

The prostate produces several proteases, the most abundant ones being kallikrein-related peptidase 3 (KLK3, PSA) and KLK2 (hK2), which are potential targets for tumor imaging and treatment. KLK3 expression is lower in malignant than in normal prostatic epithelium and it is further reduced in poorly differentiated tumors, in which the expression of KLK2 is increased. KLK3 has been shown to inhibit angiogenesis, whereas KLK2 may mediate tumor growth and invasion by participating in proteolytic cascades. Thus, it may be possible to control prostate cancer growth by modulating the proteolytic activity of KLK3 and KLK2. We have developed peptides that very specifically stimulate the activity of KLK3 or inhibit that of KLK2. Using these peptides we have established peptide-based methods for the determination of enzymatically active KLK3. The first-generation peptides are unstable in vivo and are rapidly cleared from the circulation. Currently we are modifying the peptides to make them suitable for in vivo applications. We have been able to considerably improve the stability of KLK2-binding peptides by cyclization. In this review we summarize the possible roles of KLK3 and KLK2 in prostate cancer and then concentrate on the development of peptides that modulate the activity of these proteases.

Keywords: hK2; kallikrein; peptide modification; phage display; prostate cancer; PSA

Citing Articles

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[1]
Johanna M. Mattsson, Pirjo Laakkonen, Ulf‐Håkan Stenman, and Hannu Koistinen
Scandinavian Journal of Clinical and Laboratory Investigation, 2009, Volume 69, Number 4, Page 447
[2]
Konstantinos Mavridis, Margaritis Avgeris, and Andreas Scorilas
Expert Opinion on Therapeutic Targets, 2014, Volume 18, Number 4, Page 365
[3]
Kristian Meinander, Miikka Pakkala, Janne Weisell, Ulf-Håkan Stenman, Hannu Koistinen, Ale Närvänen, and Erik A. A. Wallén
ACS Medicinal Chemistry Letters, 2014, Volume 5, Number 2, Page 162
[4]
Zhiqun Shang, Yuanjie Niu, Qiliang Cai, Jing Chen, Jing Tian, Shuyuan Yeh, Kuo-Pao Lai, and Chawnshang Chang
Tumor Biology, 2014, Volume 35, Number 3, Page 1881
[5]
Kristian Meinander, Janne Weisell, Miikka Pakkala, Andrew C. Tadd, Can Hekim, Roope Kallionpää, Kim Widell, Ulf-Håkan Stenman, Hannu Koistinen, Ale Närvänen, Jouko Vepsäläinen, Kristina Luthman, and Erik A. A. Wallén
MedChemComm, 2013, Volume 4, Number 3, Page 549
[6]
Johanna M. Mattsson, Ale Närvänen, Ulf-Håkan Stenman, and Hannu Koistinen
The Prostate, 2012, Volume 72, Number 14, Page 1588
[7]
Henna H. Härkönen, Johanna M. Mattsson, Juha A. E. Määttä, Ulf-Håkan Stenman, Hannu Koistinen, Sanni Matero, Björn Windshügel, Antti Poso, and Maija Lahtela-Kakkonen
ChemMedChem, 2011, Volume 6, Number 12, Page 2170
[8]
Joakim E. Swedberg, Simon J. de Veer, and Jonathan M. Harris
Biological Chemistry, 2010, Volume 391, Number 4
[9]
Lina Chen, Qian Wang, Liangcai Zhang, Jingxie Tai, Hong Wang, Wan Li, Xu Li, Weiming He, and Xia Li
Molecular BioSystems, 2011, Volume 7, Number 4, Page 1033
[10]
Johanna M. Mattsson, Pirjo Laakkonen, Sami Kilpinen, Ulf-Håkan Stenman, and Hannu Koistinen
Biological Chemistry, 2008, Volume 389, Number 6
[11]
Can Hekim, Tero Riipi, Lei Zhu, Pirjo Laakkonen, Ulf-HÃ¥kan Stenman, and Hannu Koistinen
The Prostate, 2009, Page n/a

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