Comparative study on synthesis of conotoxins by hydrophobic carrier assisted liquid phase method and solid phase method
Objective To study the synthesis and identification of three disulfide bond isomers of conotoxins.Methods The linear peptides of μ-CnIIIC-Ⅰ,μ-CnIIIC-Ⅱ and μ-CnIIIC-Ⅲ were 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-Ⅱand μ-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 charac-terized by mass spectrometry;the average yields of μ-CnIIIC-Ⅰ,μ-CnIIIC-Ⅱ,μ-CnIIIC-Ⅲwere15.64%,13.27%,10.56%by SPPS method and LPPS method 18.45%,17.62%,15.37%;the average consumption of 1 g μ-CnIIIC-Ⅰ,μ-CnIIIC-Ⅱ,μ-CnIIIC-Ⅲ by 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 and12.72 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.
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