普兰林肽的合成新方法  

A New Method for the Synthesis of Pramlintide

作　　者：杨晓婧[1] 赵红玲[1] 尹志峰[1] 王良友[1] 张森 寇成[3] 

机构地区：[1]承德医学院,河北承德067000 [2]河北威远动物药业有限公司,河北石家庄050011 [3]河北民族师范学院,河北承德067000

出　　处：《河北民族师范学院学报》2015年第2期60-64,共5页Journal of Hebei Normal University For Nationalities

摘　　要：首先,通过合理的分析,将普兰林肽长链分割为7个短肽链。以Fmoc氨基酸为起始原料,首先通过液相合成法,合成7个短肽链化合物。然后采用Fmoc固相合成法,以Amide Rink MBHA树脂做载体,以HBTU/HO Bt/DIEA做缩合剂,逐步缩合得到全保护线性普兰林肽树脂。用碘氧化半胱氨酸的巯基形成二硫键。以TFA的混合溶剂裂解脱除保护基团得到粗品。最后,通过反相制备液相纯化得到98%以上的普兰林肽产品。该工艺总收率为37%。液相固相组合合成的方法操作简单,效率高,成本低,收率高,产品纯度高,更适合于工业化生产。First of all, the long chain of pramlintide is divided into seven short peptide chains based on rea-sonable analysis. Taking amino acids protected by Fmoc-as original material, the seven short peptide chains are obtained with the Liquid-Phase Synthesis Method. Then fully protected linear pramlintide-resins is completed step by step by using Fmoc-Solid-Phase Synthesis Method which is carried by Amide Rink MBHA resin, with HBTU/HOBt/DIEA as condensing reagent. A disulfide bond is formed between thiols of two cysteines by oxidation of iodine. A crude product is obtained after removing the protecting group in a mixed solvent including TFA. At last the pramlintid which has more than 98% purity is obtained by purification with Reversed Phase Preparative Liquid Chromatography. The total yield of this technology is 37%. In summary, the combination method technolo-gy of liquid and solid phase synthesis is simple with high efficiency The high purity products with low cost and high yield is most suitable for industrial production.

关 键 词：普兰林肽 液相合成法 固相合成法 二巯键 

分 类 号：O6[理学—化学]