Total Synthesis of the Spider-Venom Peptide Hi1a
Nisharnthi M. Duggan, Natalie J. Saez, Daniel Clayton, Elena Budusan, Emma E. Watson, Isaac J. Tucker, Lachlan D. Rash, Glenn F. King, Richard J. Payne
Abstract
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.
Topics & Concepts
VenomChemistryPeptideSpider toxinNative chemical ligationSpiderNeuroprotectionPeptide synthesisRecombinant DNALigationCombinatorial chemistryPharmacologyBiochemistryStereochemistryChemical synthesisIn vitroReceptorMolecular biologyBiologyEcologyGlutamate receptorGeneIon channel regulation and functionNeurobiology and Insect Physiology ResearchIon Transport and Channel Regulation