神经降压素的固相合成工艺研究

Technology of Solid-Phase Synthesis of Neurotensin

神经降压素是由13个氨基酸残基组成的生物活性多肽,具有多重生理功能,且高活性、作用快速,可作为潜在的安定药、镇痛药和降压药等,具有广阔的应用前景。本研究主要进行了神经降压素固相合成的工艺研究。以Fmoc保护的氨基酸为原料,Wang树脂为载体,按照神经降压素的氨基酸序列,从C端向N端进行合成。考察了缩合试剂、脱保护试剂、脱出树脂等条件对合成效果的影响,确定了合成工艺:以二氯甲烷(DCM)为反应溶剂,O-苯并三氮唑-N,N,N′,N′-四甲基脲四氟硼酸酯(TBTU)/1-羟基苯并三氮唑(HOBT)/N,N-二异丙基乙胺(DIEA)为缩合体系,采用(三氟乙酸(TFA)/H2O/甲基苯基硫醚(thioanisole)/Phenol/乙二硫醇(EDT)体系,体积比为82∶5∶5∶6∶2的下树脂条件,2倍过量保护氨基酸进行缩合反应,反应时间为3h。反应结果使神经降压素粗品的收率达61.8%,纯度达46%。

Neurotensin（NT） is a kind of bioactive peptide which is composed of 13 amino acids. It has multifunctions, especially in pain relieving and blood hypertension. Thus it has broad applications as potential nerve medicines in the field of medicial area. NT was synthesized successfully from C-terminal to N-terminal according to the amino acids sequence with the raw material of Fmoc-amino acids and Wang resin as the vector. The influences of combination, deblock and cleavage reagents on the final result of synthesis were discussed. The optimized technology of NT synthesis was as follows： using DCM as the coupling solvent, TBTU/HOBT/DIEA as the coupling reagent, resin with TFA/H2O/thioanisole/Phenol/EDT （Volune ratio of 82： 5：5：6：2） as the cleavage condition, the reaction time 3 h. The yield of crude product was 61.8%, the purity of the product was 46 %.