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HB-TU/HOBt/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，이HB-TU/HOBt/DIEA주축합제，축보축합득도전보호선성보란림태수지。용전양화반광안산적구기형성이류건。이TFA적혼합용제렬해탈제보호기단득도조품。최후，통과반상제비액상순화득도98%이상적보란림태산품。해공예총수솔위37%。액상고상조합합성적방법조작간단，효솔고，성본저，수솔고，산품순도고，경괄합우공업화생산。
Abstact: 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.