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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Rational development of a strategy for modifying the aggregatibility of proteins
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Rational development of a strategy for modifying the aggregatibility of proteins

机译：合理开发修改蛋白质聚集性的策略

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摘要

The conversion of peptide and proteins from their soluble state into well-organized aggregates, together with the accompanied oxidation of methionine residue, presents a significant challenge to human health, to the manufacture of protein therapeutics, and to the synthesis of proteins and glycoproteins. Despite their fundamental importance, little is known about the molecular basis of these two side reactions and their control. Here, using chemical peptide synthesis, we further confirmed the importance of the balance between hydrophobic interactions and electrostatic repulsive forces in inducing and inhibiting aggregation and methionine oxidation. Most importantly, through extending the established principle, we are able to effectively stabilize the problematic peptide fragment through the attachment of cleavable arginine tags. Future applications of our approach are expected to facilitate the synthesis and study of difficult peptides, proteins, and glycoproteins and will provide more opportunities for the optimization of protein biopharmaceuticals and for the development of cell-permeable biomolecules.
机译：肽和蛋白质从其可溶状态到组织良好的聚集体的转化以及蛋氨酸残基的伴随氧化，对人类健康，蛋白质治疗剂的生产以及蛋白质和糖蛋白的合成提出了重大挑战。尽管它们具有根本的重要性，但对这两个副反应的分子基础及其控制知之甚少。在这里，使用化学肽合成，我们进一步证实了疏水相互作用和静电排斥力之间的平衡在诱导和抑制聚集和蛋氨酸氧化中的重要性。最重要的是，通过扩展已建立的原理，我们能够通过连接可裂解的精氨酸标签来有效稳定有问题的肽片段。我们方法的未来应用有望促进困难肽，蛋白质和糖蛋白的合成和研究，并将为蛋白质生物药物的优化和细胞可渗透生物分子的开发提供更多机会。

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  • 作者

    Zhongping Tan; Shiying Shang; Samuel J. Danishefsky;

  • 作者单位

    Bio-Organic Chemistry Laboratory, Molecular Pharmacology and Chemistry Program, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021;

    Bio-Organic Chemistry Laboratory, Molecular Pharmacology and Chemistry Program, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021;

    Bio-Organic Chemistry Laboratory, Molecular Pharmacology and Chemistry Program, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021 Department of Chemistry, Columbia University, New York, NY 10027;

  • 收录信息 美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

    erythropoietin; liquid chromatography; mass spectrometry;

    机译：促红细胞生成素液相色谱质谱;

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