Chinese Journal of Organic Chemistry >
DIC/Oxyma Based Efficient Synthesis and Activity Evaluation of Spider Peptide Toxin GsMTx4
Received date: 2021-09-01
Revised date: 2021-09-21
Online published: 2021-10-21
Supported by
National Natural Science Foundation of China(21807063); National Natural Science Foundation of China(82003647); National Natural Science Foundation of China(22177058); China Postdoctoral Science Foundation(2019M652307); China Postdoctoral Science Foundation(2020T130332); Natural Science Foundation of Shandong Province(ZR2019BH045); Natural Science Foundation of Shandong Province(ZR2020QH100)
Coupling reagents mediate the formation of amide bonds and play a key role in solid phase peptide synthesis. The novel N,N-diisopropylcarbodiimide (DIC)/ethyl cyanoglyoxylate-2-oxime (Oxyma) condensation system has the advantages of low cost, operational safety, higher coupling efficiency and lower rate of racemization. The DIC/Oxyma condensation system has been widely used in manual and automated synthesis of peptides. However, the ideal reaction ratio in DIC/Oxyma condensation system at mild reaction temperature remains to be further investigated. GsMTx4 is a cysteine rich peptide toxin identified from the venom of Grammostola spatulata spider, which consists of 34 amino acid residues and three pairs of disulfide bonds. GsMTx4 is the only inhibitor specifically targeting piezo channel, which is a multifunctional mechanically sensitive cation channel and associated with a variety of hereditary diseases. Herein, the synthetic efficiencies of different reaction ratios of DIC and Oxyma at moderate reaction temperature were systematically evaluated. The efficiency and robustness of DIC/Oxyma condensation system were validated by the rapid manual synthesis of linear GsMTx4. The one-step oxidative folding strategy was applied for the construction of three pairs of disulfide bridges, affording the active GsMTx4. The circular dichroism and patch-clamp electrophysiology tests were conducted to evaluate the structure and activity of synthetic GsMTx4. In summary, a fast, robust and safe synthetic method based on DIC/Oxyma is established, which is particularly useful for the manual synthesis of peptides.
Key words： DIC; Oxyma; solid phase peptide synthesis; disulfide bond; oxidative folding; GsMTx4; peptide toxin
Yannan Ma , Ya'ni Liu , Jinyan Wang , Xitong Chen , Hao Yin , Qiaona Chi , Shixi Jia , Shanshan Du , Yunkun Qi , Kewei Wang . DIC/Oxyma Based Efficient Synthesis and Activity Evaluation of Spider Peptide Toxin GsMTx4[J]. Chinese Journal of Organic Chemistry, 2022 , 42(2) : 498 -506 . DOI: 10.6023/cjoc202109003
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