人脑利钠肽的Fmoc固相合成

探讨生物活性肽人脑利钠肽(BNP)的固相合成工艺,并为工业化合成提供理论依据.本文以二氯三甲基树脂(以下简称为二氯树脂)为载体,采用9-芴甲氧羰基(Fmoc)保护的氨基酸,以1-氧-3-双二甲胺羰基苯骈三氮唑四氟化硼盐(TBTU)/1-羟基苯并三氮唑(HOBT)/二异丙基乙胺(DIEA)缩合,以碘作为环化试剂,用切割试剂将BNP粗品从树脂上切割下来.通过MALDI-MS质谱仪检测,所合成环肽的分子量与理论分子量一致,使用RP-HPLC液相色谱仪对合成的环肽进行纯化,得到的BNP纯度达到97%以上.本合成工艺具有快捷、简便、高效的特点,适合于大批量的生产目的肽.

Fmoc Solid-phase Synthesis of Natriuretic Peptide in the Human Brain

To discuss a new method of synthesis of cyclopeptide and to establish a theoretical Basis of synthesis of cyclopeptide in industry, The synthesis based on the solid-phase synthesis with 2-Chlorotrityl Chloride Resin as solid supporter, HBTU/HOBT/DIEA as the coupling reagent, I2 as the cyclizing agent. After condensation and cleaved by HBTU/HOBT/DIEA and TFA-H20, the cyclopeptide BNP was cut from the 2-Chlorotrityl Chloride Resin, The result of MALDI-MS shows that the molecular weight of the cyclopeptide was 3463.59, which is according with the theoretical molecular weight of the BNP. The cyclopeptide was then purified by RP-HPLC with the purity more than 97%. The new method is simple, convenient, and high efficiency, so it can be applied in synthesis a great deal of polypeptide.