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Design of potent, non-toxic anticancer peptides based on the structure of the antimicrobial peptide, temporin-1CEa

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Abstract

Recent advances in the search for novel anticancer agents have indicated that the positively charged antimicrobial peptides have emerged as promising agents offering several advantages over the conventional anticancer drugs. As a naturally occurring, cationic, α-helical antimicrobial peptide, temproin-1CEa has been proved to exhibit a potent anticancer effect and a moderate hemolytic activity. In order to reduce the hemolytic activity of temporin-1CEa and improve its anticancer potency towards a range of human breast cancer cells, in the present study, six analogs of temporin-1CEa were rationally designed and synthesized. The amphipathicity levels and α-helical structural patterns of peptides were reserved, while their cationic property and hydrophobicity were changed. The results of MTT and hemolysis assay indicated that the analog peptides displayed an improved anticancer activity and showed an overall optimized therapeutic index. The hydrophobicity of peptides was positively correlated with their hemolytic and antitumor activities. Moreover, the data suggest a strategy of increasing the cationicity while maintaining the moderate hydrophobicity of naturally occurring amphipathic α-helical peptides to generate analogs with improved cytotoxicity against tumor cells but decreased activity against non-neoplastic cells such as human erythrocytes. This work highlights the potential for rational design and synthesis of improved antimicrobial peptides that have the capability to be used therapeutically for treatment of cancers.

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Acknowledgments

This work was supported by the National Natural Science Foundation of China (81202448 and 31272314), Scientific Research Fund of Liaoning Provincial Education Department (L2012382) and the Program for Liaoning Innovative Research Team in University (LT2012019).

Conflict of interest

The authors declare that there are no conflict of interest.

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Authors and Affiliations

  1. Liaoning Provincial Key Laboratory of Biotechnology and Drug Discovery, Liaoning Normal University, Dalian, 116029, China

    Qing-Zhu Yang, Che Wang, Lei Lang, He Wang & De-Jing Shang

  2. Faculty of Chemistry and Chemical Engineering, Liaoning Normal University, Dalian, 116029, China

    Che Wang & Yang Zhou

  3. Faculty of Life Science, Liaoning Normal University, Dalian, 116029, China

    De-Jing Shang

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  1. Qing-Zhu Yang
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  2. Che Wang
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  3. Lei Lang
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  4. Yang Zhou
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  5. He Wang
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  6. De-Jing Shang
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Correspondence to Che Wang or De-Jing Shang.

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Yang, QZ., Wang, C., Lang, L. et al. Design of potent, non-toxic anticancer peptides based on the structure of the antimicrobial peptide, temporin-1CEa. Arch. Pharm. Res. 36, 1302–1310 (2013). https://doi.org/10.1007/s12272-013-0112-8

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  • DOI: https://doi.org/10.1007/s12272-013-0112-8

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