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Synthesis and evaluation of tumor-homing peptides for targeting prostate cancer

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Abstract

High toxicity caused by chemotherapeutic drugs and the acquisition of drug resistance by cancer cells are the major drawbacks in cancer therapy. A promising approach to overcome the posed barriers is conjugating tumor-homing peptides to drugs or nanocarriers. Such high-affinity peptides can specifically target surface markers overexpressed by cancer cells, ensuring a rapid and cancer-specific uptake of the drugs. Since prostate-specific membrane antigen (PSMA) is overexpressed by aggressive prostate cancer cells, targeting this surface protein with peptide conjugates can lead to the development of effective strategies against prostate cancer. In this study, we aimed to determine which PSMA-binding peptide among peptides 563, 562 and 9-mer, show the highest selectivity towards PSMA using 22Rv1 prostate cancer cells, a cell line with moderate PSMA levels. Tumor-homing peptides were synthesized by fluorenylmethoxycarbonyl-based solid-phase peptide synthesis (Fmoc-SPPS) strategy, and evaluated for their prostate cancer cell-specific targeting efficiencies by flow cytometry. Our results showed that the PSMA-binding capacity of peptide 563 was superior to those of 562, 9-mer, and 5-mer; therefore, can be utilized as a potent-targeting agent not only in the treatment of high PSMA positive but also moderate PSMA positive prostate cancer tumors.

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Acknowledgements

We would like to thank Ayla Burcin Asutay for her technical support in flow cytometry.

Funding

This study is funded by TÜBİTAK under Grant number 315S049.

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Authors and Affiliations

  1. Department of Genetics and Bioengineering, Yeditepe University, 34755, Istanbul, Turkey

    Ayca Ece Nezir & Dilek Telci

  2. Department of Chemistry, Yozgat Bozok University, 66900, Yozgat, Turkey

    Melek Parlak Khalily

  3. Department of Chemistry, Middle East Technical University, 06800, Ankara, Turkey

    Melek Parlak Khalily & Salih Ozcubukcu

  4. Materials Institute, Marmara Research Center, TUBITAK, 41470, Kocaeli, Turkey

    Sevgi Gulyuz & Ozgur Yilmaz

  5. Department of Chemistry, Faculty of Science and Letters, Istanbul Technical University, 34469, Istanbul, Turkey

    Sevgi Gulyuz

  6. Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Marmara University, 34668, Istanbul, Turkey

    Ş. Güniz Küçükgüzel

Authors
  1. Ayca Ece Nezir
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  2. Melek Parlak Khalily
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  3. Sevgi Gulyuz
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  4. Salih Ozcubukcu
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  5. Ş. Güniz Küçükgüzel
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  6. Ozgur Yilmaz
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  7. Dilek Telci
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Correspondence to Dilek Telci.

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Handling editor: E. Agostinelli.

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Nezir, A.E., Khalily, M.P., Gulyuz, S. et al. Synthesis and evaluation of tumor-homing peptides for targeting prostate cancer. Amino Acids 53, 645–652 (2021). https://doi.org/10.1007/s00726-021-02971-3

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  • DOI: https://doi.org/10.1007/s00726-021-02971-3

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