DIC/Oxyma‐based accelerated synthesis and oxidative folding studies of centipede toxin RhTx. (12th September 2021)

• Record Type: Journal Article
• Authors: Chen, Xi‐Tong; Wang, Jin‐Yan; Ma, Yan‐Nan; Dong, Li‐Ying; Jia, Shi‐Xi; Yin, Hao; Fu, Xing‐Yan; Du, Shan‐Shan; Qi, Yun‐Kun; Wang, KeWei
• Is Part Of: Journal of peptide science. Volume 28:Number 3(2022)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2021-09-12
• Subjects: DIC -- disulfide bond -- oxidative folding -- Oxyma -- RhTx -- solid‐phase peptide synthesis; Peptides -- Periodicals; Peptides -- Periodicals; 572.65
• DOI: 10.1002/psc.3368
• Languages: English
• ISSNs: 1075-2617

Abstract

Abstract : Coupling reagents play crucial roles in the iterative construction of amide bonds for the synthesis of peptides and peptide‐based derivatives. The novel DIC/Oxyma condensation system featured with the low risk of explosion displayed remarkable abilities to inhibit racemization, along with efficient coupling efficiency in both manual and automated syntheses. Nevertheless, an ideal reaction molar ratio in DIC/Oxyma condensation system and the moderate reaction temperature by manual synthesis remain to be further investigated. Herein, the synthetic efficiencies of different reaction ratios between DIC and Oxyma under moderate reaction temperature were systematically evaluated. The robustness and efficiency of DIC/Oxyma condensation system are validated by the rapid synthesis of linear centipede toxin RhTx. Different folding strategies were applied for the construction of disulfide bridges in RhTx, which was further confirmed in assays of circular dichroism and patch‐clamp electrophysiology evaluation. This work establishes the DIC/Oxyma‐based accelerated synthesis of peptides under moderate condensation conditions, which is especially useful for the manual synthesis of peptides. Besides, the strategy presented here provides robust technical supports for the large‐scale synthesis and oxidative folding of RhTx. Abstract : This work establishes the DIC/Oxyma‐based accelerated synthesis of peptides under moderate condensation conditions, which is especially useful for the manual synthesis of peptides. Besides, this strategy provides robust technical supports for the large‐scale synthesis and oxidative folding of RhTx. It is anticipated that the comparative studies of different folding strategies may provide a beneficial reference for future preparations of disulfide‐containing peptides.