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International Journal of Peptides
Volume 2011 (2011), Article ID 834525, 10 pages
http://dx.doi.org/10.1155/2011/834525
Research Article

In Vitro Selection of Cathepsin E-Activity-Enhancing Peptide Aptamers at Neutral pH

1Department of Functional Materials Science, Graduate School of Science and Engineering, Saitama University, 255 Shimo-Okubo, Saitama 338-8570, Japan
2City Area Program Saitama Metropolitan Area, Saitama Small and Medium Enterprises Development Corporation, 2-3-2 Kamiochiai, Chuo-Ku, Saitama 338-0001, Japan
3Rational Evolutionary Design of Advanced Biomolecules, Saitama (REDS) Group, Saitama Small Enterprise Promotion Corporation, no. 552 Saitama Industrial Technology Center, 3-12-18 Kami-Aoki, Kawaguchi, Saitama 333-0844, Japan
4Janusys Corporation, no. 508 Saitama Industrial Technology Center, 3-12-18 Kami-Aoki, Kawaguchi, Saitama 333-0844, Japan
5Proteolysis Research Laboratory, Graduate School of Pharmaceutical Sciences, Kyushu University, Higashi-Ku, Fukuoka 812-8582, Japan

Received 3 December 2010; Accepted 17 January 2011

Academic Editor: Brian Walker

Copyright © 2011 Madhu Biyani et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

The aspartic protease cathepsin E has been shown to induce apoptosis in cancer cells under physiological conditions. Therefore, cathepsin E-activity-enhancing peptides functioning in the physiological pH range are valuable potential cancer therapeutic candidates. Here, we have used a general in vitro selection method (evolutionary rapid panning analysis system (eRAPANSY)), based on inverse substrate-function link (SF-link) selection to successfully identify cathepsin E-activity-enhancing peptide aptamers at neutral pH. A successive enrichment of peptide activators was attained in the course of selection. One such peptide activated cathepsin E up to 260%, had a high affinity (KD; ∼300 nM), and had physiological activity as demonstrated by its apoptosis-inducing reaction in cancerous cells. This method is expected to be widely applicable for the identification of protease-activity-enhancing peptide aptamers.