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<p>Evidence indicates that the survivin protein is overexpressed in various types of cancer. Survivin belongs to the inhibitors of apoptosis proteins (IAPs) family, which plays a crucial role in preventing apoptosis and regulating the cell cycle. This protein has a multifaceted function in the cell cycle, particularly in regulating mitosis and cytokinesis. Survivin binds to XIAP, enhancing its stability, and interactively inhibiting caspase-9 activity. Additionally, survivin inhibits apoptosis by inactivating the Smac/DIABLO factor. In this study, we investigated the dual role of peptides in disrupting cell division and inducing apoptosis. Specifically, we designed anti-cancer peptides derived from the Borealin protein. Through single-point mutations, we developed several peptide variants and evaluated their efficacy using bioinformatics approaches, including molecular docking and molecular dynamics simulations. Based on these analyses, we identified P2 and P3 peptides as candidates with the highest binding affinities. Subsequently, the P3 was synthesized for experimental validation. By targeting key mechanisms involved in cancer cell survival and proliferation, P3 demonstrates significant potential as a novel anti-cancer agent with reduced side effects. These findings mark an important step forward in the development of more effective cancer therapies.</p>

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Computational and experimental discovery of peptide inhibitors targeting survivin for therapeutic potential in cancer

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年8月20日

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  • Seyedeh Fatemeh Ahmadi,
  • Seyed Shahriar Arab,
  • Hamidreza Samadikhah

摘要

Evidence indicates that the survivin protein is overexpressed in various types of cancer. Survivin belongs to the inhibitors of apoptosis proteins (IAPs) family, which plays a crucial role in preventing apoptosis and regulating the cell cycle. This protein has a multifaceted function in the cell cycle, particularly in regulating mitosis and cytokinesis. Survivin binds to XIAP, enhancing its stability, and interactively inhibiting caspase-9 activity. Additionally, survivin inhibits apoptosis by inactivating the Smac/DIABLO factor. In this study, we investigated the dual role of peptides in disrupting cell division and inducing apoptosis. Specifically, we designed anti-cancer peptides derived from the Borealin protein. Through single-point mutations, we developed several peptide variants and evaluated their efficacy using bioinformatics approaches, including molecular docking and molecular dynamics simulations. Based on these analyses, we identified P2 and P3 peptides as candidates with the highest binding affinities. Subsequently, the P3 was synthesized for experimental validation. By targeting key mechanisms involved in cancer cell survival and proliferation, P3 demonstrates significant potential as a novel anti-cancer agent with reduced side effects. These findings mark an important step forward in the development of more effective cancer therapies.