化学学报 ›› 2010, Vol. 68 ›› Issue (07): 667-671. 上一篇    下一篇

研究论文

半胱氨酸肽片段连接法合成ω-芋螺毒素MVIIA

代先东,范崇旭*,曹瑛,刘尚义,蒋辉,陈冀胜   

  1. (北京药物化学研究所 北京 102205)
  • 投稿日期:2009-12-23 修回日期:2010-02-23 发布日期:2010-04-14
  • 通讯作者: 范崇旭 E-mail:fancx@263.com

Synthesis of ω-Conotoxin MVIIA by Native Chemical Ligation

Dai Xiandong Fan Chongxu* Cao Ying Liu Shangyi Jiang Hui Chen Jisheng   

  1. (Beijing Institute of Pharmaceutical Chemistry, Beijing 102205)
  • Received:2009-12-23 Revised:2010-02-23 Published:2010-04-14

ω-芋螺毒素MVIIA是已上市的镇痛药Ziconotide的有效成分. 采用标准Fmoc保护策略在聚苯乙烯树脂上合成ω-MVIIA比较困难, 是固相合成中的“困难肽”. 本研究将ω-MVIIA分为N-端15肽硫酯和C-端10肽两个片段采用标准Fmoc保护策略分别合成, 再通过半胱氨酸肽片段连接得到全长的ω-芋螺毒素MVIIA肽链. 该方法提高了合成ω-芋螺毒素MVIIA产率. 该研究为“困难肽”的合成提供了较好的参考方法.

关键词: 半胱氨酸肽片段连接, 多肽硫酯, 多肽合成, ω-芋螺毒素MVIIA

ω-Conotoxin MVIIA is the main component of Ziconotide, a therapeutic drug on the market as treatment of chronic pain. It is difficult to be synthesized by using standard Fmoc strategy solid phase peptide synthesis (SPPS) on polystyrene resin. ω-MVIIA is a typical "difficult sequence" for SPPS. In this work, N-terminal 15-residue peptide thioester and C-terminal 10-residue peptide amide of ω-MVIIA were synthesized using standard Fmoc protocol respectively. The full-length chain of ω-MVIIA was prepared by native chemical ligation. This method increased the yield of ω-MVIIA greatly. The results provide a good reference for synthesis of "difficult sequence".

Key words: native chemical ligation, peptide thioester, peptide synthesis, ω-conotoxin MVIIA