Duggan, N.M.Saez, N.J.Clayton, D.Budusan, E.Watson, E.E.Tucker, I.J.Rash, L.D.King, G.F.Payne, R.J.2022-08-222022-08-222021Organic Letters, 2021; 23(21):8375-83791523-70601523-7052https://hdl.handle.net/2440/136100Hi1a is a venom peptide from the Australian funnelweb spider Hadronyche infensa with a complex tertiary structure. Hi1a has neuroprotective and cardioprotective properties due to its potent inhibition of acid-sensing ion channel 1a (ASIC1a) and is currently being pursued as a novel therapy for acute ischemic events. Herein, we describe the total synthesis of Hi1a using native chemical ligation. The synthetic peptide was successfully folded and exhibited similar inhibitory activity on ASIC1a to recombinant Hi1a.en© 2021 American Chemical SocietyAnimalsSpidersPeptidesSpider VenomsMolecular StructureAcid Sensing Ion ChannelsSpider VenomsJournal article10.1021/acs.orglett.1c031122022-08-16616217Watson, E.E. [0000-0001-5946-473X]