2. Academic Validation
  3. Synthesis of breast cancer targeting conjugate of temporin-SHa analog and its effect on pro- and anti-apoptotic protein expression in MCF-7 cells

Synthesis of breast cancer targeting conjugate of temporin-SHa analog and its effect on pro- and anti-apoptotic protein expression in MCF-7 cells

  • Peptides. 2018 Aug:106:68-82. doi: 10.1016/j.peptides.2018.07.002.
Farzana Shaheen 1,  Muhammad Nadeem-Ul-Haque 2,  Aqeel Ahmed 3,  Shabana U Simjee 4,  A Ganesan 5,  Almas Jabeen 3,  Zafar Ali Shah 2,  M Iqbal Choudhary 4
Affiliations

Affiliations

  • 1 H. E. J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi, 75270, Pakistan. Electronic address: afnan.iccs@gmail.com.
  • 2 H. E. J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi, 75270, Pakistan.
  • 3 Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences, University of Karachi, Karachi, 75270, Pakistan.
  • 4 H. E. J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi, 75270, Pakistan; Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences, University of Karachi, Karachi, 75270, Pakistan.
  • 5 School of Pharmacy, University of East Anglia, Norwich Research Park, Norwich NR4 7TJ, United Kingdom.
PMID: 30026168 DOI: 10.1016/j.peptides.2018.07.002
Abstract

The frog natural product temporin-SHa (FLSGIVGMLGKLFamide) is a potent antimicrobial peptide, as is the analog [S3K]SHa. By solid-phase synthesis, we prepared temporin-SHa and several temporin-SHa analogs with one or more D-alanine residues incorporated. The natural product and the analog [G10a]SHa were found to be cytotoxic in mammalian cell lines and induce cell death. To achieve selectivity, we conjugated the analog [G10a]SHa with a breast Cancer targeting peptide (BCTP). The resulting peptide temporin [G10a]SHa-BCTP conjugate was selectively active against the MCF-7 breast Cancer cell line with no cytotoxicity in NIH-3T3 fibroblasts. Unlike the natural product or [G10a]SHa, the conjugated peptide induced Apoptosis, downregulating the expression of Bcl-2 and Survivin and upregulating Bax and Caspase-3.

Keywords

Antimicrobial peptides; Apoptosis; Bcl-2; Breast cancer targeting peptide conjugate; Survivin; caspase-3; temporin-SHa analogs.

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