Comparison of different strategies towards the chemical synthesis of long‐chain scorpion toxin AaH‐II. (31st August 2021)

• Record Type: Journal Article
• Authors: Li, Yu‐Lei; Qu, Qian; Qi, Yun‐Kun; Liu, Lei; Wang, Ke Wei; Liu, Yani; Fang, Ge‐Min
• Is Part Of: Journal of peptide science. Volume 28:Number 2(2022)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2021-08-31
• Subjects: AaH‐II -- native chemical ligation -- peptide hydrazide -- peptide synthesis -- scorpion venoms; Peptides -- Periodicals; Peptides -- Periodicals; 572.65
• DOI: 10.1002/psc.3365
• Languages: English
• ISSNs: 1075-2617

Abstract

Abstract : Long‐chain scorpion toxin AaH‐II isolated from Androctonus australis Hector can selectively inhibit mammalian voltage‐gated sodium ion channel Nav 1.7 responsible for pain sensation. Efficient chemical synthesis of AaH‐II and its derivatives is beneficial to the study of the function and mechanism of Nav 1.7 and the development of potential peptide inhibitors. Herein, we compared three different strategies, namely, direct solid‐phase peptide synthesis, hydrazide‐based two‐segment native chemical ligation, and hydrazide‐based three‐segment native chemical ligation for the synthesis of AaH‐II. The hydrazide‐based two‐segment native chemical ligation affords the target toxin with the optimal efficiency, which provides a practically robust procedure for the preparation of tool molecules derived from AaH‐II to study the biological functions and modulation of Nav 1.7. Our work highlights the importance of selecting suitable segment condensation approach in the chemical synthesis of protein toxins. Abstract : We compared three different strategies, namely, direct solid‐phase peptide synthesis, hydrazide‐based two‐ or three‐segment native chemical ligation for the synthesis of AaH‐II. The hydrazide‐based two‐segment native chemical ligation provides a practically robust procedure for the preparation of tool molecules derived from AaH‐II.