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Antitumor activity of novel chimeric peptides derived from cyclinD/CDK4 and the protein transduction domain 4

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Abstract

CyclinD1/CDK4 and cyclinD3/CDK4 complexes are key regulators of the cell progression and therefore constitute promising targets for the design of anticancer agents. In the present study, the key peptide motifs were selected from these two complexes. Chimeric peptides with these peptides conjugated to the protein transduction domain 4 (PTD4) were designed and synthesized. The chimeric peptides, PTD4-D1, PTD4-D3, PTD4-K4 exhibited significant anti-proliferation effects on cancer cell lines. These peptides could compete with the cyclinD/CDK4 complex and induce the G1/S phase arrest and apoptosis of cancer cells. In the tumor challenge experiment, these peptides showed potent antitumor effects with no significant side effects. Our results suggested that these peptides could be served as novel leading compounds with potent antitumor activity.

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Acknowledgments

This work was supported by grants from the National Natural Science Foundation of China (Nos. 30901362, 81172893, 81000673) and the National Science and Technology Major Projects of New Drugs (2012ZX09103301-023).

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The authors declare that there are no conflicts of interest.

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Authors and Affiliations

  1. Department of Bioengineering, Zhengzhou University, 100 Science Road, Zhengzhou, 450001, China

    Haili Wang, Yanping Chen, Lei Sun, Guodong Li, Mingxia Zhai, Wenjie Zhai, Qiaozhen Kang, Yanfeng Gao & Yuanming Qi

  2. Second Affiliated Hospital, Harbin Medical University, Harbin, 150086, China

    Xi Chen

  3. Eugenics Genetic Research Laboratory, Henan Provincal Research Institute for Family Planning, Zhengzhou, 450002, China

    Haili Wang

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  1. Haili Wang
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  2. Xi Chen
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  5. Guodong Li
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Correspondence to Yanfeng Gao or Yuanming Qi.

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Haili Wang and Xi Chen contributed equally to this work.

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Wang, H., Chen, X., Chen, Y. et al. Antitumor activity of novel chimeric peptides derived from cyclinD/CDK4 and the protein transduction domain 4. Amino Acids 44, 499–510 (2013). https://doi.org/10.1007/s00726-012-1360-5

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  • DOI: https://doi.org/10.1007/s00726-012-1360-5

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