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Halogen Bonding: A Powerful Tool for Modulation of Peptide Conformation

机译:卤素键合:用于调制肽构象的强大工具

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摘要

Halogen bonding is a weak chemical force that has so far mostly found applications in crystal engineering. Despite its potential for use in drug discovery, as a new molecular tool in the direction of molecular recognition events, it has rarely been assessed in biopolymers. Motivated by this fact, we have developed a peptide model system that permits the quantitative evaluation of weak forces in a biologically relevant proteinlike environment and have applied it for the assessment of a halogen bond formed between two amino acid side chains. The influence of a single weak force is measured by detection of the extent to which it modulates the conformation of a cooperatively folding system. We have optimized the amino acid sequence of the model peptide on analogues with a hydrogen bond-forming site as a model for the intramolecular halogen bond to be studied, demonstrating the ability of the technique to provide information about any type of weak secondary interaction. A combined solution nuclear magnetic resonance spectroscopic and computational investigation demonstrates that an interstrand halogen bond is capable of conformational stabilization of a beta-hairpin foldamer comparable to an analogous hydrogen bond. This is the first report of incorporation of a conformation-stabilizing halogen bond into a peptide/protein system, and the first quantification of a chlorine-centered halogen bond in a biologically relevant system in solution.
机译:卤素键是迄今为止在晶体工程中发现的弱化学力。尽管它有可能用于药物发现,但作为分子识别事件方向的新分子工具,它很少在生物聚合物中进行评估。通过这一事实,我们开发了一种肽模型系统,允许在生物相关的蛋白质状环境中定量评估弱力的弱力,并应用于评估两条氨基酸侧链之间形成的卤素键。通过检测它调节协作折叠系统的构象的程度来测量单个弱力的影响。我们已经优化了用氢键 - 形成部位的类似物的模型肽的氨基酸序列作为待研究的分子内卤素键的模型,证明了该技术提供了有关任何类型的弱二次相互作用的信息的能力。组合的溶液核磁共振光谱和计算研究表明,Interstrand卤素键能够构成与类似氢键相当的β-发夹粘膜体的稳定化。这是第一报告将构象稳定的卤素键掺入肽/蛋白质体系中,并在溶液中生物相关系统中的氯中心卤素键的第一定量。

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  • 来源
    《Biochemistry》 |2017年第25期|共8页
  • 作者单位

    Univ Gothenburg Dept Chem &

    Mol Biol SE-41296 Gothenburg Sweden;

    Univ Gothenburg Dept Chem &

    Mol Biol SE-41296 Gothenburg Sweden;

    Univ Gothenburg Dept Chem &

    Mol Biol SE-41296 Gothenburg Sweden;

    Univ Gothenburg Dept Chem &

    Mol Biol SE-41296 Gothenburg Sweden;

    Univ Gothenburg Dept Chem &

    Mol Biol SE-41296 Gothenburg Sweden;

    Univ Gothenburg Dept Chem &

    Mol Biol SE-41296 Gothenburg Sweden;

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  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 生物化学;
  • 关键词

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