Abstract
Subtractive cell surface panning from phage random peptide library and molecular docking were used to select and find binding peptides dual-targeting MMP14 and metal ions on MG-63 cells. Phages were abundantly enriched and totally 22 different peptide sequences were obtained. We demonstrated that the affinity phage peptides were not only targeted to MMP14 but also had affinities for zinc and nickel ions. Four possible peptide consensus sequences were identified as: AHQ/SLH/P, L/I/EPLL/I, T/Q/DARH/FQ, MK/PSR. The representative peptides were found to dock well to MMP14 at the sites around aa. 120–125 which were also the catalytic region of zinc binding sites on MMP14 by MVD molecular docking. The selected monoclonal phages could efficiently bind to the MMP14 expressed MG-63 cells and this again confirmed the targeting binding of the peptides to MMP14. In vitro study revealed that the selected monoclonal phages could greatly inhibit the viability of MG-63 cells. Also, the four synthetic representative consensus peptides inhibited the viability of MG-63 and HepG2 cells at μg levels. The consensus sequences identified in our study were newly reported and relatively specific to MMP14 and this may be further used for MMP14 based peptide drug development and/or diagnostic analyses.
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Acknowledgments
The work was financially supported by the Program of the Fundamental Research Funds for the Central Universities of China (SWJTU09ZT28 to Canquan Mao) and National High Technology Research and Development Program of China (National 863, 2006AAZ353 to Canquan Mao).
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First two authors contributed equally to this work and are joint first authors.
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Liang, Z., Huang, J., Huang, T. et al. Selection and Finding of Lead Peptides Dual-targeting MMP14 and Metal Ions by Subtractive Cell Surface Panning and Molecular Docking. Int J Pept Res Ther 18, 31–40 (2012). https://doi.org/10.1007/s10989-011-9276-6
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DOI: https://doi.org/10.1007/s10989-011-9276-6