高等学校化学学报 ›› 2016, Vol. 37 ›› Issue (9): 1643-1648.doi: 10.7503/cjcu20160237

• 有机化学 • 上一篇    下一篇

异肽键稳定的MERS-CoV融合蛋白S2亚基N端重复序列三股α螺旋的构建

郑汐, 梁国栋, 王潮(), 刘克良()   

  1. 军事医学科学院毒物药物研究所, 抗毒药物与毒理学国家重点实验室, 北京 100850
  • 收稿日期:2016-04-13 出版日期:2016-09-10 发布日期:2016-08-26
  • 作者简介:联系人简介: 刘克良, 男, 博士, 研究员, 博士生导师, 主要从事多肽药物、 核酸化学及药用高分子材料研究. E-mail:keliangliu55@126.com;王 潮, 男, 博士, 助理研究员, 主要从事多肽药物研究. E-mail:chaow301@gmail.com
  • 基金资助:
    国家自然科学基金(批准号: 81373266, 81573266)资助

Construction of Isopeptide Bridge-tethered NHR-trimeric Coiled-coil in MERS-CoV Membrane Fusion Protein

ZHENG Xi, LIANG Guodong, WANG Chao*(), LIU Keliang*()   

  1. Beijing Institute of Pharmacology and Toxicology, State Key Laboratory of Toxicology and Medical Countermeasures, Beijing 100850, China
  • Received:2016-04-13 Online:2016-09-10 Published:2016-08-26
  • Contact: WANG Chao,LIU Keliang E-mail:chaow301@gmail.com;keliangliu55@126.com
  • Supported by:
    † Supported by the National Natural Science Foundation of China(Nos.81373266, 81573266)

摘要:

通过在天然N肽的氨基端引入可以诱导螺旋三聚体形成的人工多肽序列, 并通过酰基转移反应在上述嵌合肽所形成的三股α螺旋间引入异肽键, 构建了中东呼吸综合征病毒(MERS-CoV)的N-trimer模型, 为MERS-CoV融合抑制剂的设计奠定了基础.

关键词: 中东呼吸综合征病毒, 融合蛋白, 多肽, 异肽键

Abstract:

In Middle East respiratory syndrome coronavirus(MERS-CoV) infection, the formation of a coiled-coil six-helical bundle(6-HB) between three C-terminal heptad repeats(CHRs) and an N-terminal heptad repeat(NHR) trimer of the MERS-CoV spike protein S2 subunit provided the energy necessary for virus-cell membrane fusion. Mimicry of the NHR-helical trimers in the MERS-CoV membrane fusion protein for the discovery of antiviral therapeutics hampered because of the strong aggregation properties of synthetic NHR-based peptides taken out of their parent protein structure. Herein, the article presents an efficient strategy to recapi-tulate MERS-CoV NHR α-helical trimers via combining the concepts of grafting the NHR-derived peptides onto an exogenous trimerization motif with stabilization of the trimeric oligomers through isopeptide bonds. The covalent bridge was introduced by an acyl transfer reaction between lysine and glutamic acid in specific amino acid sites with thio-easter modified. The designed isopeptide bridge-stabilized chimeric trimers has strong potential for the development potent MERS-CoV fusion inhibitors.

Key words: Middle East respiratory syndrome coronavirus, Fusion protein, Peptide, Isopeptide bond

中图分类号: