Rapid Chemical Synthesis of Neuroprotective Hi1a
Hi1a is a venom peptide isolated from the Australian funnel-web spider <i>Hadronyche infensa</i>, 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.
Authors
- Stephen A. Byrne (ORCID: https://orcid.org/0000-0002-2098-409X)
- Andrei Loas (ORCID: https://orcid.org/0000-0001-5640-1645)
- Bradley L. Pentelute (ORCID: https://orcid.org/0000-0002-7242-801X)
- Giulio Fittolani (ORCID: https://orcid.org/0000-0001-6201-3454)
- Daniel G. Anderson (ORCID: https://orcid.org/0000-0003-0151-4903)
- Julien Couture‐Senécal (ORCID: https://orcid.org/0000-0002-6370-5839)
- Charlotte E. Farquhar (ORCID: https://orcid.org/0000-0003-4919-2296)
- Elee Shimshoni (ORCID: https://orcid.org/0000-0003-3057-5393)
Institutions
- Broad Institute (US)
- Center for Environmental Health (US)
- Harvard–MIT Division of Health Sciences and Technology (US)
- Artificial Intelligence in Medicine (Canada) (CA)
- Koch Institute for Integrative Cancer Research At MIT (US)
- Massachusetts Institute of Technology (US)
Publication Details
- Journal
- The Journal of Organic Chemistry
- Published
- 2025-10-13
- DOI
- https://doi.org/10.1021/acs.joc.5c01533
- Primary Topic
- Receptor Mechanisms and Signaling
- Type
- article
- Field-Weighted Citation Impact
- 0.00