HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 281, Issue 18, 12555-12560, May 5, 2006

This Article Full Text Full Text (PDF) All Versions of this Article: 281/18/12555    most recent M600014200v1 Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Hekim, C. Articles by Stenman, U.-H. Search for Related Content PubMed PubMed Citation Articles by Hekim, C. Articles by Stenman, U.-H. Social Bookmarking                      What's this?

Novel Peptide Inhibitors of Human Kallikrein 2^*

Can Hekim¹, Jari Leinonen¹, Ale Närvänen, Hannu Koistinen, Lei Zhu, Erkki Koivunen^¶, Ville Väisänen^||, and Ulf-Håkan Stenman²

From the Department of Clinical Chemistry, Helsinki University Central Hospital, Biomedicum, FIN-00290 Helsinki, Finland, Department of Chemistry, University of Kuopio, FIN-70211 Kuopio, Finland, ^¶Department of Biosciences, Division of Biochemistry, University of Helsinki, FIN-00014 Helsinki, Finland, and ^||Department of Biotechnology, University of Turku, FIN-20520 Turku, Finland

Human kallikrein 2 (hK2) is a serine protease produced by the secretory epithelial cells in the prostate. Because hK2 activates several factors participating in proteolytic cascades that may mediate metastasis of prostate cancer, modulation of the activity of hK2 is a potential way of preventing tumor growth and metastasis. Furthermore, specific ligands for hK2 are potentially useful for targeting and imaging of prostate cancer and for assay development. We have used enzymatically active recombinant hK2 captured by a monoclonal antibody exposing the active site of the enzyme to screen phage display peptide libraries. Using libraries expressing 10 or 11 amino acids long linear peptides, we identified six different peptides binding to hK2. Three of these were shown to be specific and efficient inhibitors of the enzymatic activity of hK2 toward a peptide substrate. Furthermore, the peptides inhibited the activation of the proform of prostate-specific antigen by hK2. Amino acid substitution analyses revealed that motifs of six amino acids were required for the inhibitory activity. These peptides are potentially useful for treatment and targeting of prostate cancer.

Received for publication, January 3, 2006 , and in revised form, March 2, 2006.

^* This work was supported by the grants from National Technology Agency of Finland, University of Helsinki, Helsinki University Central Hospital, the Finnish Cancer Foundation, the Academy of Finland, Juselius Foundation, and Finska Läkaresällskapet. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ These authors contributed equally to this study.

² To whom correspondence should be addressed: Dept. of Clinical Chemistry, P. O. Box 700, 00029 Helsinki University Central Hospital, Finland. Tel.: 358-9-47171738; Fax: 358-9-47171737; E-mail: ulf-hakan.stenman{at}hus.fi.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				R. K. Nam, W. W. Zhang, L. H. Klotz, J. Trachtenberg, M. A.S. Jewett, J. Sweet, A. Toi, S. Teahan, V. Venkateswaran, L. Sugar, et al. Variants of the hK2 Protein Gene (KLK2) Are Associated with Serum hK2 Levels and Predict the Presence of Prostate Cancer at Biopsy. Clin. Cancer Res., November 1, 2006; 12(21): 6452 - 6458. [Abstract] [Full Text] [PDF]