dc.contributor.author | Lynagh, Timothy | |
dc.contributor.author | Kiontke, Stephan | |
dc.contributor.author | Meyhoff-Madsen, Maria | |
dc.contributor.author | Gless, Bengt H. | |
dc.contributor.author | Johannesen, Jónas | |
dc.contributor.author | Kattelmann, Sabrina | |
dc.contributor.author | Christiansen, Anders | |
dc.contributor.author | Dufva, Martin | |
dc.contributor.author | Laustsen, Andreas H. | |
dc.contributor.author | Devkota, Kanchan | |
dc.contributor.author | Olsen, Christian A. | |
dc.contributor.author | Kümmel, Daniel | |
dc.contributor.author | Pless, Stephan Alexander | |
dc.contributor.author | Lohse, Brian | |
dc.date.accessioned | 2021-06-24T06:38:50Z | |
dc.date.available | 2021-06-24T06:38:50Z | |
dc.date.created | 2021-01-27T11:54:50Z | |
dc.date.issued | 2020 | |
dc.identifier.issn | 0022-2623 | |
dc.identifier.uri | https://hdl.handle.net/11250/2760985 | |
dc.description | Copyright 2020 American Chemical Society | en_US |
dc.description.abstract | Venomous snakebites cause >100 000 deaths every year, in many cases via potent depression of human neuromuscular signaling by snake α-neurotoxins. Emergency therapy still relies on antibody-based antivenom, hampered by poor access, frequent adverse reactions, and cumbersome production/purification. Combining high-throughput discovery and subsequent structure–function characterization, we present simple peptides that bind α-cobratoxin (α-Cbtx) and prevent its inhibition of nicotinic acetylcholine receptors (nAChRs) as a lead for the development of alternative antivenoms. Candidate peptides were identified by phage display and deep sequencing, and hits were characterized by electrophysiological recordings, leading to an 8-mer peptide that prevented α-Cbtx inhibition of nAChRs. We also solved the peptide:α-Cbtx cocrystal structure, revealing that the peptide, although of unique primary sequence, binds to α-Cbtx by mimicking structural features of the nAChR binding pocket. This demonstrates the potential of small peptides to neutralize lethal snake toxins in vitro, establishing a potential route to simple, synthetic, low-cost antivenoms. | en_US |
dc.language.iso | eng | en_US |
dc.publisher | American Chemical Society | en_US |
dc.rights | Navngivelse 4.0 Internasjonal | * |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/deed.no | * |
dc.title | Peptide Inhibitors of the α‑Cobratoxin−Nicotinic Acetylcholine Receptor Interaction | en_US |
dc.type | Journal article | en_US |
dc.type | Peer reviewed | en_US |
dc.description.version | publishedVersion | en_US |
cristin.ispublished | true | |
cristin.fulltext | original | |
cristin.qualitycode | 2 | |
dc.identifier.doi | 10.1021/acs.jmedchem.0c01202 | |
dc.identifier.cristin | 1880245 | |
dc.source.journal | Journal of Medicinal Chemistry | en_US |
dc.source.pagenumber | 13709-13718 | en_US |
dc.identifier.citation | Journal of Medicinal Chemistry. 2020, 63 (22), 13709-13718. | en_US |
dc.source.volume | 63 | en_US |
dc.source.issue | 22 | en_US |