CAJ | 학술논문

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。
수선,통과합리적분석,장보란림태장련분할위7개단태련。이Fmoc안기산위기시원료,수선통과액상합성법,합성7개단태련화합물。연후채용Fmoc고상합성법,이Amide Rink MBHA수지주재체,이HBTU/HO Bt/DIEA주축합제,축보축합득도전보호선성보란림태수지。용전양화반광안산적구기형성이류건。이TFA적혼합용제렬해탈제보호기단득도조품。최후,통과반상제비액상순화득도98%이상적보란림태산품。해공예총수솔위37%。액상고상조합합성적방법조작간단,효솔고,성본저,수솔고,산품순도고,경괄합우공업화생산。
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.