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Design, synthesis and biological evaluation of novel peptides as potential agents with anti-tumor and multidrug resistance-reversing activities

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Abstract

Tumor chemotherapy is an important mean in the clinical treatment of metastatic cancer,but low selectivity and drug resistance restrict its clinical application. BP100 is a multifunctional membrane-active peptide with high antimicrobial activity. We selected BP100 as a lead peptide, designed and synthesized a series of BP100 analogs through solid-phase synthesis. Amongst them, peptides with the Tyr10 residue substituted by leucine and histidine showed the highest anti-cancer activity. Further experiments revealed that BP100 and its analogs could disrupt the cell membrane and trigger the cytochrome C release into cytoplasm, which ultimately resulted in apoptosis. Meanwhile, BP100 and its analogs also exhibited effective anti-tumor activity against multidrug-resistant cells, showing multidrug resistance-reversing effects. In conclusion, these peptides might be promising candidates for cancer therapy.

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Acknowledgements

This study was supported by Grants from the National Natural Science Foundation of China (Grants 81673299 and 81273376).

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Author notes

  1. Bo Zhang and Wei Shi contributed equally to this work.

Authors and Affiliations

  1. Center of Drug Discovery, State Key Laboratory of Natural Medicines, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing, 210009, People’s Republic of China

    Bo Zhang, Wei Shi, Jieming Li, Chen Liao, Mingxue Li, Wenlong Huang & Hai Qian

  2. Jiangsu Key Laboratory of Drug Discovery for Metabolic Disease, China Pharmaceutical University, 24 Tongjiaxiang,, Nanjing, 210009, People’s Republic of China

    Wenlong Huang & Hai Qian

Authors
  1. Bo Zhang
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  2. Wei Shi
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  3. Jieming Li
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  4. Chen Liao
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  5. Mingxue Li
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  6. Wenlong Huang
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  7. Hai Qian
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Correspondence to Wenlong Huang or Hai Qian.

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Handling Editor: G. J. Peters.

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Zhang, B., Shi, W., Li, J. et al. Design, synthesis and biological evaluation of novel peptides as potential agents with anti-tumor and multidrug resistance-reversing activities. Amino Acids 49, 1355–1364 (2017). https://doi.org/10.1007/s00726-017-2434-1

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  • DOI: https://doi.org/10.1007/s00726-017-2434-1

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