奥曲肽固相合成工艺研究

Study on solid-phase synthetic process of octreotide

目的优化奥曲肽固相合成工艺。方法本研究采用Fmoc保护基固相合成策略合成奥曲肽直链肽[D-Phe-Cys-Phe-D-Trp-Lys-Thr-Cys-Thr(ol)],并在此基础上进行裂解、成环、纯化、制备奥曲肽。本研究着重对裂解条件进行优化,包括裂解液成分、比例、反应温度和时间等。结果与结论以TFA∶TIS∶H_(2)O∶DTT=90∶2.5∶2.5∶8为裂解体系,在10℃下反应2~3 h得到纯度92%(HPLC)的直链肽粗品。本文优化的裂解条件提高了奥曲肽直链肽纯度,同时避免了乙二硫醇的使用,使得生产过程对环境更加友好,更适合工业化生产。

Octreotide is a derivative of artificially modified natural somatostatin, which has a great market prospect.However, the purity of its linear peptide is still not high enough.Therefore, this study made some improvements in the cleavage method of linear peptide.The cleavage conditions, including composition, ratio, reaction temperature and time, were adjusted according to literatures.Finally, the result showed that a combination of TFA,TIS,H_(2)O and DTT in a ratio of 90∶2.5∶2.5∶8 was the best cleavage system, and 10 ℃ for 2-3 h gave the product with highest purity, thus improving the yield, quality and reducing the production cost of octreotide.Also, the method avoided the use of ethanedithiol, which made the production process more environment-friendly.