Solid-phase synthesis method of Ziconotide

一种齐考诺肽的固相合成方法

Abstract

本发明公开了一种齐考诺肽的固相合成方法,以Fmoc-氨基树脂为固相载体,缩合反应连接25个侧链保护的氨基酸,得到线性全保护肽树脂,其中,形成二硫键的三组Cys分别连接Trt、Acm或tBu保护基;将树脂进行线性切割,切割的同时脱去除Cys(Acm)和Cys(tBu)外的其它所有氨基酸的侧链保护基;氧化线性肽形成第一对二硫键,得到单二硫环肽;脱除单二硫环肽中Cys(Acm)的Acm保护基,同时环化形成第二对二硫键,得到双二硫环肽;脱除双二硫环肽中Cys(tBu)的tBu保护基,同时环化形成第三对二硫键,得到三二硫环肽;三二硫环肽经纯化、冻干得到齐考诺肽。
The invention discloses a solid-phase synthesis method of Ziconotide. The method comprises the following steps of: performing condensation reaction by taking Fmoc-amino resin as a solid-phase carrier and connecting 25 side chain protected amino acids to obtain linear fully protected resin, wherein three groups of Cys which form disulfide bonds are connected with Trt, Acm or tBu protecting groups respectively; linearly cutting the resin and removing the side chain protected groups of other amino acids except for Cys(Acm) and Cys(tBu); oxidizing linear peptide to form the first pair of disulfide bonds to obtain single disulfide cyclopeptide; removing the Acm protected group of the Cys(Acm) from the single disulfide cyclopeptide and cyclizing to form the second pair of disulfide bonds to obtain double disulfide cyclopeptide; removing the tBu protected group of the Cys(tBu) from the double disulfide cyclopeptide and cyclizing to form the third pair of disulfide bonds to obtain triple disulfide cyclopeptide; and purifying and freeze-drying the triple disulfide cyclopeptide to obtain the Ziconotide.

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Patent Citations (2)

    Publication numberPublication dateAssigneeTitle
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NO-Patent Citations (1)

    Title
    曹本文: "选择性氧化形成三对二硫键合成齐考诺肽", 《合成化学》, vol. 19, no. 1, 31 January 2011 (2011-01-31), pages 145 - 147

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    CN-104974229-AOctober 14, 2015泰州施美康多肽药物技术有限公司Linaclotide solid-phase synthesis method