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• W2105447530 abstract "The growth factor receptor-bound protein Src homology 2 (Grb2-SH2) plays an important role in the oncogenic Ras signaling pathway, which involves in cell proliferation and differentiation. Therefore, the antagonist of Grb2-SH2 has become a potential target for developing anticancer agents. Recently, we discovered the peptide 1 (Fmoc-Glu-Tyr-Aib- Asn-NH2) with high affinity for the Grb2-SH2 domain by using surface plasmon resonance (SPR)-biosensor technology. Herein, we report the further design of the lead peptide 1 by addition of an Arg-Gly-Asp sequence to 1 to enhance its binding to Grb2-SH2 and to induce apoptosis in cancer cells. Both the linear and cyclic analogs of the newly designed compounds were prepared along with an analog in which the Nα-Fmoc group was removed. These peptide analogs were assayed for their affinity for the Grb2-SH2, their antiproliferative effect on human breast cancer cells, their specificity for cancer cells, and their effects on cytotoxicity and the cell cycle. MCF-7 and MDA-MB-453 breast cancer cells were treated with various concentrations of each peptide. The cell viability and cytotoxicity of peptide-treated cells were determined by using the cell proliferation kit (3-[4, 5-dimethyl-2-thiazolyl]-2, 5-diphenyl-tetrazolium bromide, MTT) and cytotoxicity kit (lactate dehydrogenase, LDH), respectively. Effects of peptides on the cell cycle progression of cancer cells and apoptosis were analyzed by using flow cytometry. Results demonstrated that the peptide analog 2 (H-Arg-Gly-Asp- Glu-Tyr-Aib-Asn-Arg-Gly-Asp-NH2) had anti-proliferative effects on MCF-7 and MDA-MB-453 cells with the IC50 of 45.7 μM and 47.4 μM, respectively. The cytotoxicity and percentage of sub-G1 in the cell cycle were increased in these cancer cells when cells were treated with higher concentration of the Arg-Gly-Asp-containing peptide 2. These results provide important information for the development of anti-cancer agents. Keywords: Peptide, human breast cancer cell line, cell viability, cytotoxicity, cell cycle, apoptosis" @default.
• W2105447530 created "2016-06-24" @default.
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• W2105447530 date "2010-01-01" @default.
• W2105447530 modified "2023-10-09" @default.
• W2105447530 title "Effects of Peptidic Antagonists of Grb2-SH2 on Human Breast Cancer Cells" @default.
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• W2105447530 doi "https://doi.org/10.2174/092986610789909421" @default.
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