疏水载体辅助液相法与固相法合成芋螺毒素的工艺对比  

Comparative study on synthesis of conotoxins by hydrophobic carrier assisted liquid phase method and solid phase method

作　　者：张文杰 张发进 赵仕法 董玉香 郭凯 姬胜利 ZHANG Wenjie;ZHANG Fajin;ZHAO Shifa;DONG Yuxiang;GUO Kai;JI Shengli(ReaLi Tide Biological technology(Weihai)Co.,Ltd,Weihai 264402,Shandong,P.R.China;College of Pharmacy,Binzhou Medical University,Yantai 264003,Shandong,P.R.China)

机构地区：[1]润辉生物技术(威海)有限公司,山东威海264402 [2]滨州医学院药学院,山东烟台264003

出　　处：《滨州医学院学报》2024年第2期94-101,共8页Journal of Binzhou Medical University

基　　金：山东省重点研发计划(重大科技创新工程)(2021CXGC010501)。

摘　　要：目的对芋螺毒素μ-CnIIIC的三种二硫键异构体进行合成工艺研究及表征鉴定。方法通过可溶性疏水载体辅助液相合成法(LPPS)和固相多肽合成法(SPPS)人工合成μ-CnIIIC的三种二硫键异构体的线性肽,采用三步氧化法对线性肽进行氧化折叠,获得三种折叠肽异构体(μ-CnIIIC-Ⅰ、μ-CnIIIC-Ⅱ和μ-CnIIIC-Ⅲ),并对两种合成工艺进行物料消耗量、“三废”产生量、收率进行对比。结果成功合成芋螺毒素异构体并进行了质谱表征;采用SPPS法和LPPS法合成μ-CnIIIC-Ⅰ、μ-CnIIIC-Ⅱ、μ-CnIIIC-Ⅲ平均收率为15.64%、13.27%、10.56%和18.45%、17.62%、15.37%;采用SPPS法和LPPS法合成1 gμ-CnIIIC-Ⅰ、μ-CnIIIC-Ⅱ、μ-CnIIIC-Ⅲ物料平均消耗量为20.65、21.62、24.78 g和61.19、72.17、90.75 g,平均废液产生量分别为1.49、1.57、1.78 L和12.72、15.00、19.16 L。SPPS法和LPPS法比较差异均有统计学意义(P<0.05)。结论通过对芋螺毒素μ-CnIIIC异构体的合成研究,表明LPPS法的总体收率比SPPS法收率高且物料消耗量及“三废”产生量少,因此LPPS法具有重大的研究意义和商业价值。Objective To study the synthesis and identification of three disulfide bond isomers of conotoxins.Methods The linear peptides ofμ-CnIIIC-Ⅰ,μ-CnIIIC-Ⅱandμ-CnIIIC-Ⅲwere synthesized by soluble hydrophobic carrier assisted liquid-phase synthesis(LPPS)and solid-phase peptide synthesis(SPPS).Three fold peptide isomers(μ-CnIIIC-Ⅰ,μ-CnIIIC-Ⅱandμ-CnIIIC-Ⅲ)were obtained by three-step oxidative folding of the linear peptides,and we compared the material consumption,"three wastes"production and yield of the two synthetic processes.Results Conotoxin were successfully synthesized and characterized by mass spectrometry;the average yields ofμ-CnIIIC-Ⅰ,μ-CnIIIC-Ⅱ,μ-CnIIIC-Ⅲwere 15.64%,13.27%,10.56%by SPPS method and LPPS method 18.45%,17.62%,15.37%;the average consumption of 1 gμ-CnIIIC-Ⅰ,μ-CnIIIC-Ⅱ,μ-CnIIIC-Ⅲby SPPS method and LPPS method is 20.65 g,21.62 g,24.78 g and 61.19 g,72.17 g,90.75 g,and the average waste liquid yields were 1.49 L,1.57 L,1.78 L and 12.72 L,15.00 L,19.16 L,respectively.The difference between SPPS method and the LPPS method was statistically significant(P<0.05).Conclusion The synthesis of conotoxin isomers showed that the overall yield of LPPS method is higher than that of SPPS method,and the consumption of material and the production of"three wastes"were less.Therefore,LPPS method has great research significance and commercial value.

关 键 词：多肽 可溶性疏水载体辅助液相合成法 固相多肽合成法 tag-OH 

分 类 号：R943[医药卫生—药剂学]