半胱氨酸肽片段连接法合成ω-芋螺毒素MVIIA

Synthesis of ω-Conotoxin MVIIA by Native Chemical Ligation

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.

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＂.