Chinese Journal of Organic Chemistry ›› 2021, Vol. 41 ›› Issue (7): 2800-2809.DOI: 10.6023/cjoc202102045 Previous Articles     Next Articles



王金艳a, 董黎颖a, 刘雅妮a, 陈西同a, 马艳楠a, 尹昊a, 杜姗姗b,*(), 齐昀坤a,*(), 王克威a   

  1. a 青岛大学药学院 山东青岛 266073
    b 青岛科技大学化工学院 山东青岛 266042
  • 收稿日期:2021-02-24 修回日期:2021-03-24 发布日期:2021-04-12
  • 通讯作者: 杜姗姗, 齐昀坤
  • 作者简介:
    † 共同第一作者(These authors contributed equally to this work).
  • 基金资助:
    国家自然科学基金(21807063); 国家自然科学基金(82003647); 国家自然科学基金(81870653); 中国博士后科学基金(2019M652307); 中国博士后科学基金(2020T130332); 山东省自然科学基金(ZR2019BH045); 山东省自然科学基金(ZR2020QH100)

Efficient Synthesis and Oxidative Folding Studies of Centipede Toxin RhTx

Jinyan Wanga, Liying Donga, Ya'ni Liua, Xitong Chena, Yannan Maa, Hao Yina, Shanshan Dub(), Yunkun Qia(), Kewei Wanga   

  1. a School of Pharmacy, Qingdao University, Qingdao, Shandong 266073
    b College of Chemical Engineering, Qingdao University of Science and Technology, Qingdao, Shandong 266042
  • Received:2021-02-24 Revised:2021-03-24 Published:2021-04-12
  • Contact: Shanshan Du, Yunkun Qi
  • Supported by:
    National Natural Science Foundation of China(21807063); National Natural Science Foundation of China(82003647); National Natural Science Foundation of China(81870653); China Postdoctoral Science Foundation(2019M652307); China Postdoctoral Science Foundation(2020T130332); Natural Science Foundation of Shandong Province(ZR2019BH045); Natural Science Foundation of Shandong Province(ZR2020QH100)

The critical step for the synthesis of disulfide-containing peptides is the efficient construction of one or multiple disulfide bridges. Generally, the folding of disulfide bonds could be achieved by three chemical strategies,i.e. one-step oxidative folding strategy, multi-step oxidative folding strategy, and one-pot oxidative folding strategy. Because few comparative studies have been conducted on efficiencies of three strategies, the systematical research is desirable. Three folding strategies were separately applied for the preparation of centipede toxin RhTx. The results showed that the isolated yield of two-step oxidative folding strategy was higher than those of one-step and one-pot oxidative folding strategies. Besides, the one-pot oxidative folding strategy may induce severe misfoldings. The circular dichroism (CD) and activity tests indicated that disulfide bonds are critical for the structure and activity of RhTx. In addition, the efficient preparation of RhTx on tens of milligrams scale was achieved, affording molecular tools for the further biological and biophysical studies of RhTx targeting TRPV1. Overall, three mainstream oxidative folding strategies were systematically studied, which provided a valuable reference for the synthesis of disulfide-containing peptides.

Key words: disulfide bond, disulfide-containing peptide, oxidative folding, RhTx, solid phase peptide synthesis, thiol protecting group