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Probing the interaction between cisplatin and the therapeutic monoclonal antibody trastuzumab

机译：探讨顺铂与治疗单克隆抗体曲妥珠单抗的相互作用

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摘要

Trastuzumab (Herceptin) is a fully humanized monoclonal immunoglobulin gamma-1 (IgG1) antibody directed against the HER2/neu receptor, which is up-regulated in about 20-25% of gastric and breast cancer patients. The combination of trastuzumab with cisplatin results in a favourable toxicity profile in the case of advanced HER2-positive gastric and gastroesophageal cancers, gaining the approval by the U.S. FDA in 2010. However, the current literature reveals no atomic details about platinum drug-trastuzumab interactions, probably because of size limitations. Our research aim has been to probe the interaction between the monoclonal antibody trastuzumab and cisplatin by means of electrospray mass spectrometry analysis within the "divide and conquer" approach and H-1, N-15-HSQC NMR spectroscopy (using N-15-labeled cisplatin). We demonstrate that trastuzumab is able to bind platinum and that there is no involvement of the residues belonging to the antigen-binding region so that the receptor recognition is not affected.
机译：在胃癌和乳腺癌的患者的约20-25％的曲妥单抗（赫赛汀）是完全人源化单克隆免疫球蛋白γ-1（IgG1的）针对HER2 / neu受体，其是抗体上调。在晚期HER2阳性胃癌和胃癌症的情况下有利的毒性轮廓顺铂结果曲妥珠单抗的组合，获得美国FDA在2010年批准。然而，目前的文献揭示了铂类药物曲妥珠单抗的相互作用没有原子细节由于尺寸限制的可能。我们的研究目的一直是探测单克隆抗体曲妥单抗和由“分而治之”的方法和H-1内电喷雾质谱法分析的手段顺铂，N-15-HSQC NMR光谱（使用N-15标记之间的相互作用顺铂）。我们表明，曲妥珠单抗能够绑定白金和没有属于这样的受体识别不受影响抗原结合区中残基的参与。

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  • 来源
    《RSC Advances》 |2016年第35期|共8页
  • 作者

    Lasorsa Alessia; Losacco Maurizio; Iacobazzi Rosa Maria; Porcelli Letizia; Azzariti Amalia; Natile Giovanni; Arnesano Fabio;

  • 作者单位

    Univ Bari Aldo Moro Dept Chem Via E Orabona 4 I-70125 Bari Italy;

    Univ Bari Aldo Moro Dept Chem Via E Orabona 4 I-70125 Bari Italy;

    Univ Bari Aldo Moro Dept Pharmacy Drug Sci Via E Orabona 4 I-70125 Bari Italy;

    Ist Tumori IRCCS Giovanni Paolo II Viale O Flacco 65 I-70124 Bari Italy;

    Ist Tumori IRCCS Giovanni Paolo II Viale O Flacco 65 I-70124 Bari Italy;

    Univ Bari Aldo Moro Dept Chem Via E Orabona 4 I-70125 Bari Italy;

    Univ Bari Aldo Moro Dept Chem Via E Orabona 4 I-70125 Bari Italy;

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  • 正文语种 eng
  • 中图分类 化学;
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