神经降压素的固相合成工艺研究

摘要神经降压素是由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%。

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	吴蕾
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关键词：神经降压素固相合成工艺研究

Abstract： Neurotensin(NT)is a kind of bioactive peptide which is composed of 13 amino acids.It has multi-functions,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/H_2O/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%.

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Received 2009-07-15; published 2009-07-15

引用本文:

吴蕾;任云霞;景文鹏;.神经降压素的固相合成工艺研究[J]. 化学工业与工程, 2009,26(4): 292-297

WU Lei,REN Yun-xia,JING Wen-peng.Technology of Solid-Phase Synthesis of Neurotensin[J]. Chemcial Industry and Engineering, 2009,26(4): 292-297

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