神经保护Hi1a的快速化学合成。

IF 3.6 2区化学 Q1 CHEMISTRY, ORGANIC

Journal of Organic Chemistry Pub Date : 2025-10-13 DOI:10.1021/acs.joc.5c01533

Stephen A Byrne,Giulio Fittolani,Elee Shimshoni,Charlotte E Farquhar,Julien Couture-Senécal,Andrei Loas,Daniel G Anderson,Bradley L Pentelute

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引用次数: 0

摘要

Hi1a是从澳大利亚漏斗网蜘蛛Hadronyche infensa中分离出来的一种毒液肽，含有复杂的“双结”三级结构，目前正在研究用于治疗缺血性中风。Hi1a的重组表达和化学合成仍然是一个重大挑战，因为繁琐的协议，延迟了转化到临床的进展。我们描述了Hi1a（76个氨基酸，AA）的首次单次化学合成，使用自动快速流动肽合成（AFPS），实现快速获取（10 mg）。这项工作强调了AFPS作为一项技术的实用性，该技术可以通过重组方法获得具有挑战性的生物分子的化学生产。

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Rapid Chemical Synthesis of Neuroprotective Hi1a.

Hi1a is a venom peptide isolated from the Australian funnel-web spider Hadronyche infensa, containing an intricate "double knot" tertiary structure, and is currently under investigation for the treatment of ischemic stroke. The recombinant expression and chemical synthesis of Hi1a remain a significant challenge due to laborious protocols, delaying progress in translation to the clinic. We describe the first single-shot chemical synthesis of Hi1a (76 amino acids, AA) using automated fast-flow peptide synthesis (AFPS), enabling rapid access (<4.5 h total synthesis time) to milligram quantities of linear Hi1a (>10 mg). This work highlights the utility of AFPS as a technology that enables chemical production of biomolecules challenging to obtain by recombinant methods.

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来源期刊

Journal of Organic Chemistry 化学-有机化学

CiteScore

6.20

自引率

11.10%

发文量

1467

审稿时长

2 months

期刊介绍： Journal of Organic Chemistry welcomes original contributions of fundamental research in all branches of the theory and practice of organic chemistry. In selecting manuscripts for publication, the editors place emphasis on the quality and novelty of the work, as well as the breadth of interest to the organic chemistry community.