Synthesis of breast cancer targeting conjugate of temporin-SHa analog and its effect on pro- and anti-apoptotic protein expression in MCF-7 cells.
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.
['Shaheen|Farzana|F|', 'Nadeem-Ul-Haque|Muhammad|M|', 'Ahmed|Aqeel|A|', 'Simjee|Shabana U|SU|', 'Ganesan|A|A|', 'Jabeen|Almas|A|', 'Shah|Zafar Ali|ZA|', 'Choudhary|M Iqbal|MI|']
D016475:3T3 Cells D000818:Animals D023181:Antimicrobial Cationic Peptides D000970:Antineoplastic Agents D017209:Apoptosis D001943:Breast Neoplasms D016923:Cell Death D006367:HeLa Cells D006801:Humans D061986:MCF-7 Cells D051379:Mice D060327:Solid-Phase Synthesis Techniques
temporin-SHa analogs Antimicrobial peptides Apoptosis Bcl-2 Survivin caspase-3 Breast cancer targeting peptide conjugate