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环肽palicourein的溶液结构:对药物框架开发的启示

Solution structure of the cyclotide palicourein: implications for the development of a pharmaceutical framework.

作者信息

Barry Daniel G, Daly Norelle L, Bokesch Heidi R, Gustafson Kirk R, Craik David J

机构信息

Institute for Molecular Bioscience, Queensland Bioscience Precinct, The University of Queensland Brisbane, Queensland 4072, Australia.

出版信息

Structure. 2004 Jan;12(1):85-94. doi: 10.1016/j.str.2003.11.019.

DOI:10.1016/j.str.2003.11.019
PMID:14725768
Abstract

The cyclotides are a family of disulfide-rich proteins from plants. They have the characteristic structural features of a circular protein backbone and a knotted arrangement of disulfide bonds. Structural and biochemical studies of the cyclotides suggest that their unique physiological stability can be loaned to bioactive peptide fragments for pharmaceutical and agricultural development. In particular, the cyclotides incorporate a number of solvent-exposed loops that are potentially suitable for epitope grafting applications. Here, we determine the structure of the largest known cyclotide, palicourein, which has an atypical size and composition within one of the surface-exposed loops. The structural data show that an increase in size of a palicourein loop does not perturb the core fold, to which the thermodynamic and chemical stability has been attributed. The cyclotide core fold, thus, can in principle be used as a framework for the development of useful pharmaceutical and agricultural bioactivities.

摘要

环肽是一类来自植物的富含二硫键的蛋白质。它们具有环状蛋白质主链和二硫键的打结排列的特征结构。环肽的结构和生化研究表明,它们独特的生理稳定性可用于生物活性肽片段的药物和农业开发。特别是,环肽包含许多潜在适用于表位嫁接应用的溶剂暴露环。在这里,我们确定了已知最大的环肽——帕利库林的结构,它在一个表面暴露环内具有非典型的大小和组成。结构数据表明,帕利库林环大小的增加不会干扰其核心折叠结构,而其热力学和化学稳定性归因于该核心折叠结构。因此,环肽核心折叠原则上可作为开发有用的药物和农业生物活性的框架。

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Solution structure of the cyclotide palicourein: implications for the development of a pharmaceutical framework.环肽palicourein的溶液结构:对药物框架开发的启示
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Chemical Proteomics for Target Discovery of Head-to-Tail Cyclized Mini-Proteins.用于头对尾环化微型蛋白质靶点发现的化学蛋白质组学
Front Chem. 2017 Oct 11;5:73. doi: 10.3389/fchem.2017.00073. eCollection 2017.
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Host-defense activities of cyclotides.环肽的宿主防御活性。
Toxins (Basel). 2012 Feb;4(2):139-56. doi: 10.3390/toxins4020139. Epub 2012 Feb 15.
4
Combined X-ray and NMR analysis of the stability of the cyclotide cystine knot fold that underpins its insecticidal activity and potential use as a drug scaffold.结合X射线和核磁共振分析环肽胱氨酸结折叠的稳定性,该折叠是其杀虫活性及作为药物支架潜在用途的基础。
J Biol Chem. 2009 Apr 17;284(16):10672-83. doi: 10.1074/jbc.M900021200. Epub 2009 Feb 10.
5
Structural plasticity of the cyclic-cystine-knot framework: implications for biological activity and drug design.环胱氨酸结框架的结构可塑性:对生物活性和药物设计的启示
Biochem J. 2006 Feb 15;394(Pt 1):85-93. doi: 10.1042/BJ20051691.
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