Solid phase synthesis method of ziconotide

Abstract

The invention relates to a solid phase synthesis method for ziconotide, which comprises the following steps: an Fmoc-Rink Amide-MBHA resin is taken as a solid phase carrier for program reaction; condensation reactions are orderly performed to link 25 amino acids with protecting groups to obtain a linear peptide complete-protection resin of the 25 amino acids,wherein in three groups of Cyses which form a disulfide bond, the Cyses in the same group are simultaneously linked with one of a Trt, Acm or Mob protecting group, and different groups of the Cyses are linked with different protecting groups; the protecting groups of the three groups of the Cyses are orderly removed; a cyclization reaction is performed to form a disulfide ring bond; a side chain protecting group is removed; and the resin is cut to obtain the ziconotide containing three disulfide rings. The method has the main advantages of few side products, high directive efficiency, simplicity, convenience, high yield of products, and favorability for the purification of the products.

Description

technical field [0001] The invention belongs to the technical field of biochemistry, and in particular relates to a solid phase synthesis method of ziconotide. Background technique [0002] Ziconotide chemical name: L-cysteinyl-L-lysyl-L-glycyl-L-lysyl-L-glycyl-L-alanyl-L-lysyl-L -cysteinyl-L-seryl-L-arginyl-L-leucyl-L-methionyl-L-tyrosyl-L-aspartyl-L-cysteinyl- L-cysteinyl-L-threonyl-L-glycyl-L-seryl-L-cysteinyl-L-arginyl-L-seryl-L-glycyl- L-lysyl-L-cysteinamide (1→16)(8→20)(15→25) tricyclic disulfide. [0003] The chemical structural formula is: [0004] [0005] Molecular formula: C 102 h 172 N 36 o 32 S 7 [0006] Molecular weight: 2639.13 [0007] Ziconotide is a peptide toxoid compound containing 25 amino acids and 3 disulfide bonds extracted from the South Pacific marine snail Conus magus. It can selectively act on N-type electrosensitive calcium channels in dendrites and axon terminal branches, thereby inhibiting the initial afferent of noxious stimuli....

AI Technical Summary

Problems solved by technology

[0009] Biological extraction is affected by the existing limited biological resources, the extraction process is cumbersome, the efficiency is low, and it is difficult to obtain high-purity products; the low-temperature natural cyclization reaction is thermodynamically controlled, the cyclization process is slow, the process control is more complicated, and the reaction yield Low

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