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有机化学
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有机化学 ›› 2008, Vol. 28 ›› Issue (03): 416-421. 上一篇    下一篇

研究论文

微波促进催产素和赖氨加压素环肽的固相合成

迟玉石，张惠斌*，倪帅健，黄文龙   

  1. (中国药科大学新药研究中心 南京 210009)
  • 收稿日期:2007-02-01 修回日期:2007-08-20 发布日期:2008-03-18
  • 通讯作者: 张惠斌

Solid Phase Synthesis of Cyclopeptides of Oxytocin and Lysipressin under Microwave Irradiation

CHI Yu-Shi,ZHANG Hui-Bin*,NI Shuai-Jian,HUANG Wen-Long   

  1. (Center of Drug Research, China Pharmaceutical University, Nanjing 210009)
  • Received:2007-02-01 Revised:2007-08-20 Published:2008-03-18
  • Contact: ZHANG Hui-Bin

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1113

被引次数

13 | 4

以Rink Amide-MBHA树脂为载体, 采用Fmoc/tBu正交保护固相合成策略, 运用微波照射促进, 先快速高效地合成得到载有催产素或赖氨加压素还原型多肽的树脂, 再将连接在树脂上的各还原型多肽分别在微波促进条件下和常温条件下环合形成二硫键制得环肽, 最后用Reagent K试剂将环肽从树脂上裂解下来得到目标多肽的粗品. 利用HPLC法测定不同固相环合条件下得到的多肽粗品纯度, 结果显示经微波促进固相环合得到的多肽粗品纯度明显高于常温条件下得到的多肽粗品纯度. 粗品最后经过反相制备高效液相系统纯化并冻干得到目标多肽纯品, 通过电喷雾质谱法测定了制得的还原型多肽及相应环肽的分子量, 验证了它们的结构.

关键词: 固相多肽合成, 微波促进, 环肽, 二硫键形成

A rapid and efficient microwave irradiation solid-phase synthesis method was developed for the preparation of the reduced form of oxytocin and lysipressin on Rink amide-MBHA resin by an Fmoc/t-Bu orthogonal protection strategy. The disulfide bridge of the target peptide was formed directly on resin under microwave irradiation or normal condition. The crude products of peptides were cleaved from the resin by treatment with Reagent K. The HPLC analysis showed that the purity of the crude cyclopeptide was higher under microwave irradiation than under normal condition. The crude peptides were purified by preparative RP-HPLC. The molecular weight of the synthetic peptides was confirmed by the electrospray mass spectrometry analysis.

Key words: microwave irradiation, disulfide bridge, solid phase peptide synthesis, cyclopeptide