Bioengineering of a Novel Peptide Sequence from the Venom of Conus obscurus

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dc.contributor.advisor Bingham, Jon-Paul
dc.contributor.author Wiere, Sean
dc.contributor.department Molecular Biosciences and Bioengineering
dc.date.accessioned 2022-03-03T19:56:58Z
dc.date.available 2022-03-03T19:56:58Z
dc.date.issued 2021
dc.description.degree M.S.
dc.identifier.uri http://hdl.handle.net/10125/81651
dc.subject Molecular biology
dc.subject Biology
dc.subject Molecular chemistry
dc.subject cone snails
dc.subject conotoxins
dc.subject mass spectrometry
dc.subject novel
dc.subject peptide
dc.subject post-translational modifications
dc.title Bioengineering of a Novel Peptide Sequence from the Venom of Conus obscurus
dc.type Thesis
dcterms.abstract The marine cone snail produces one of the fastest prey strikes in the animal kingdom with efficacious venom injection causing prey paralysis and death within seconds. Each snail produces hundreds of conotoxins and has been the source behind discovering and utilizing novel analgesic peptide therapeutics. In this study, we discover, isolate, and synthesize two α3/5 conotoxins derived from the milked venom of Conus obscurus: one novel (α-conotoxin ObI) and one previously found in the venom of Conus striatus (α-SI). We then generate five synthetic analogs, accompanying single and double mutations from the native α-conotoxin ObI. We integrate three post-translational modifications (PTMs) within analog development: N-terminal truncation, proline hydroxylation, and tryptophan bromination. α-Conotoxin ObI demonstrates nanomolar potency towards Poecilia reticulata (LD50) and the Homo sapiens muscle-type nAChR (EC50). Moreover, the analog α-ObI [P9K] displayed enhanced potency in both animal bioassays. The exhibited successful incorporation of 3 PTMs investigates the boundaries of peptide bioengineering in the generation of novel α-conotoxins.
dcterms.extent 96 pages
dcterms.language en
dcterms.publisher University of Hawai'i at Manoa
dcterms.rights All UHM dissertations and theses are protected by copyright. They may be viewed from this source for any purpose, but reproduction or distribution in any format is prohibited without written permission from the copyright owner.
dcterms.type Text
local.identifier.alturi http://dissertations.umi.com/hawii:11210
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