索玛鲁肽的制备

Synthesis of Semaglutide

本研究采用固液相合成法制备索玛鲁肽。固相合成法制备直链肽Aib^8,Arg^(34)GLP-1(7-37)以及脂肪侧链酰化剂,在碱性条件下用合成的脂肪链酰化剂对直链肽Lys^(26)进行修饰,得到索玛鲁肽,并通过时间分辨荧光共振能量转移免疫测定法对自制的样品进行生物活性测定。结果显示两个批次的样品生物活性相当,其EC_(50)是利拉鲁肽的1/2。该工艺原料价廉易得、收率高,易于工业化生产。

Semaglutide was synthesized by solid-liquid phase synthesis. Both the linear peptide Aib8, Arg34 GLP-1（7-37） and aliphatic side-chain acylating agent were obtained using solid-phase synthesis, and the Lys26 amino acid was subsequently modified by using the latter one in alkaline condition. A homogeneous time-solved fluorescence resonance energy transfer（TR-FRET） was performed to evaluate the bioactivities of the self-synthetic samples. The results showed that the bioactivities of the two samples from different batches were identical, and its EC50 was half of Liraglutide＇s. In conclusion, this process technology has several advantages such as cheap material and high yield in the industrial production.