{"refrec":{"BRefID":361563,"RR":"<b>Wiere, S.; Sugai, C.; Espiritu, M.J.; Aurelio, V.P.; Reyes, C.D.; Yuzon, N.; Whittal, R.M.; Tytgat, J.; Peigneur, S.; Bingham, J.-P.</b> (2022). Research into the bioengineering of a novel α-conotoxin from the milked venom of <i>Conus obscurus</i>. <i>International Journal of Molecular Sciences 23(20)</i>: 12096. <a href=\"https://dx.doi.org/10.3390/ijms232012096\" target=\"_blank\">https://dx.doi.org/10.3390/ijms232012096</a>","BEntID":359279,"PublicFlag":1,"CheckedFlag":1,"wosflag":1,"vabbflag":0,"RefStringPartII":". <i>International Journal of Molecular Sciences 23(20)</i>: 12096. <a href=\"https://dx.doi.org/10.3390/ijms232012096\" target=\"_blank\">https://dx.doi.org/10.3390/ijms232012096</a>","DocTypID":8,"DocType":"Journal article","MarineFlag":1,"FreshFlag":0,"BrackishFlag":0,"TerrestrialFlag":0,"Authorstring":"Wiere, S.; Sugai, C.; Espiritu, M.J.; Aurelio, V.P.; Reyes, C.D.; Yuzon, N.; Whittal, R.M.; Tytgat, J.; Peigneur, S.; Bingham, J.-P.","OrigTitleTranslFlag":0,"Authorstringtrunc":"Wiere, S. <i>et al.</i>","Englishabstract":"The marine cone snail produces one of the fastest prey strikes in the animal kingdom. It injects highly efficacious venom, often causing prey paralysis and death within seconds. Each snail has hundreds of conotoxins, which serve as a source for discovering and utilizing novel analgesic peptide therapeutics. In this study, we discovered, isolated, and synthesized a novel α3/5-conotoxins derived from the milked venom of <i>Conus obscurus</i> (α-conotoxin OI) and identified the presence of α-conotoxin SI-like sequence previously found in the venom of <i>Conus striatus</i>. Five synthetic analogs of the native α-conotoxin OI were generated. These analogs incorporated single residue or double residue mutations. Three synthetic post-translational modifications (PTMs) were synthetically incorporated into these analogs: <i>N</i>-terminal truncation, proline hydroxylation, and tryptophan bromination. The native α-conotoxin OI demonstrated nanomolar potency in <i>Poecilia reticulata</i> and <i>Homo</i> <i>sapiens</i> muscle-type nicotinic acetylcholine receptor (nAChR) isoforms. Moreover, the synthetic α-[P9K] conotoxin OI displayed enhanced potency in both bioassays, ranging from a 2.85 (LD<sub>50</sub>) to 18.4 (IC<sub>50</sub>) fold increase in comparative bioactivity. The successful incorporation of PTMs, with retention of both potency and nAChR isoform selectivity, ultimately pushes new boundaries of peptide bioengineering and the generation of novel α-conotoxin-like sequences.","AbstractOtherLang":null,"BibLvlCode":"AS","StandardTitle":"Research into the bioengineering of a novel α-conotoxin from the milked venom of <i>Conus obscurus</i>","OrigTitleLangCode":"en","OrigTitleLangCodeExtended":"eng","OrigTitleLangID":15,"DateLastModified":{"date":"2024-12-10 01:33:17.368041","timezone_type":1,"timezone":"+01:00"},"UserAccessRight":null,"UserAccID":null,"AuthorKeywords":"a-conotoxin; analog; bioassay; IC50; LD50; Conus obscurus; mass spectrometry; milked venom; post-translational modifications; nAChR","OtherDescriptors":null,"Notes":null,"AnaPub":2022,"MonPub":null,"DateUpdate":"2023-02-27","DateCreate":"2023-02-27","SecASFANote":null,"ConfID":null,"PeerRev":1,"VlizCoreFlag":1,"WoScode":"WOS:000872838200001","VABBcode":null,"OpenAcc":1,"DOI":"10.3390/ijms232012096"},"refs":null,"anarec":{"AnaID":361563,"PubliDate":2022,"Pagination":"12096","XtraPublOfAnaID":null,"ISBN":null,"Volume":"23","Issue":"20","BRefMon":null,"BRefMonRR":null,"BRefXtra":null,"BRefXtraRR":null,"SerBRefID":270393,"SerRR":"International Journal of Molecular Sciences. MDPI AG: Basel.  ISSN 1661-6596; e-ISSN 1422-0067","StandardTitleSer":"International Journal of Molecular Sciences","ISSN":"1661-6596","AbbrevSer":null,"StandardTitleMon":null,"StartPage":12096,"Pages":null,"ToPubliDate":null,"BRefBibLvlCode":"S","SerNotes":null},"monrec":null,"serrec":null,"relations":null,"relationsRev":null,"addrec":null,"othpubs":null,"ownerships":null,"authors":[{"AutName":"Wiere","Firstname":"Sean","Initials":"S.","Affiliation":null,"Discriminator":null,"CorporateFlag":0,"BEntID":359279,"AutID":517365,"OrderNr":1,"DegrID":null,"EditorFlag":0,"CorrespFlag":0,"IllustratorFlag":0,"ReviserFlag":0,"TranslatorFlag":0,"InsAcronym":null,"InsFSN":null,"ORCID":null,"PersID":null,"InsID":null},{"AutName":"Sugai","Firstname":"Christopher","Initials":"C.","Affiliation":null,"Discriminator":null,"CorporateFlag":0,"BEntID":359279,"AutID":517366,"OrderNr":2,"DegrID":null,"EditorFlag":0,"CorrespFlag":0,"IllustratorFlag":0,"ReviserFlag":0,"TranslatorFlag":0,"InsAcronym":null,"InsFSN":null,"ORCID":null,"PersID":null,"InsID":null},{"AutName":"Espiritu","Firstname":"Michael","Initials":"M.J.","Affiliation":null,"Discriminator":null,"CorporateFlag":0,"BEntID":359279,"AutID":517367,"OrderNr":3,"DegrID":null,"EditorFlag":0,"CorrespFlag":0,"IllustratorFlag":0,"ReviserFlag":0,"TranslatorFlag":0,"InsAcronym":null,"InsFSN":null,"ORCID":null,"PersID":null,"InsID":null},{"AutName":"Aurelio","Firstname":"Vincent","Initials":"V.P.","Affiliation":null,"Discriminator":null,"CorporateFlag":0,"BEntID":359279,"AutID":517369,"OrderNr":4,"DegrID":null,"EditorFlag":0,"CorrespFlag":0,"IllustratorFlag":0,"ReviserFlag":0,"TranslatorFlag":0,"InsAcronym":null,"InsFSN":null,"ORCID":null,"PersID":null,"InsID":null},{"AutName":"Reyes","Firstname":"Chloe","Initials":"C.D.","Affiliation":null,"Discriminator":null,"CorporateFlag":0,"BEntID":359279,"AutID":517370,"OrderNr":5,"DegrID":null,"EditorFlag":0,"CorrespFlag":0,"IllustratorFlag":0,"ReviserFlag":0,"TranslatorFlag":0,"InsAcronym":null,"InsFSN":null,"ORCID":null,"PersID":null,"InsID":null},{"AutName":"Yuzon","Firstname":"Nicole","Initials":"N.","Affiliation":null,"Discriminator":null,"CorporateFlag":0,"BEntID":359279,"AutID":517371,"OrderNr":6,"DegrID":null,"EditorFlag":0,"CorrespFlag":0,"IllustratorFlag":0,"ReviserFlag":0,"TranslatorFlag":0,"InsAcronym":null,"InsFSN":null,"ORCID":null,"PersID":null,"InsID":null},{"AutName":"Whittal","Firstname":"Randy","Initials":"R.M.","Affiliation":null,"Discriminator":null,"CorporateFlag":0,"BEntID":359279,"AutID":517372,"OrderNr":7,"DegrID":null,"EditorFlag":0,"CorrespFlag":0,"IllustratorFlag":0,"ReviserFlag":0,"TranslatorFlag":0,"InsAcronym":null,"InsFSN":null,"ORCID":null,"PersID":null,"InsID":null},{"AutName":"Tytgat","Firstname":"Jan","Initials":"J.","Affiliation":"Toxicology and Pharmacology, University of Leuven (KU Leuven)","Discriminator":null,"CorporateFlag":0,"BEntID":359279,"AutID":223897,"OrderNr":8,"DegrID":null,"EditorFlag":0,"CorrespFlag":0,"IllustratorFlag":0,"ReviserFlag":0,"TranslatorFlag":0,"InsAcronym":null,"InsFSN":"KU Leuven; Departement Farmaceutische en Farmacologische Wetenschappen; Laboratorium voor Toxicologie en Farmacologie","ORCID":null,"PersID":717,"InsID":492},{"AutName":"Peigneur","Firstname":"Steve","Initials":"S.","Affiliation":"Toxicology and Pharmacology, University of Leuven (KU Leuven)","Discriminator":null,"CorporateFlag":0,"BEntID":359279,"AutID":182911,"OrderNr":9,"DegrID":null,"EditorFlag":0,"CorrespFlag":0,"IllustratorFlag":0,"ReviserFlag":0,"TranslatorFlag":0,"InsAcronym":null,"InsFSN":"KU Leuven; Departement Farmaceutische en Farmacologische Wetenschappen; Laboratorium voor Toxicologie en Farmacologie","ORCID":"0000-0003-0504-5702","PersID":27019,"InsID":492},{"AutName":"Bingham","Firstname":"Jon-Paul","Initials":"J.-P.","Affiliation":null,"Discriminator":null,"CorporateFlag":0,"BEntID":359279,"AutID":43147,"OrderNr":10,"DegrID":null,"EditorFlag":0,"CorrespFlag":0,"IllustratorFlag":0,"ReviserFlag":0,"TranslatorFlag":0,"InsAcronym":null,"InsFSN":null,"ORCID":null,"PersID":null,"InsID":null}],"mapdetails":null,"datasets":null,"monographs":null,"monparts":null,"serparts":null,"BEntOpen":null,"BEntPrivate":null,"availability":[{"BInstID":387155,"LibID":36,"BRefID":361563,"EmbargoDate":null,"FullEmbargoDate":null,"PhysMedID":16,"hasOCRd":1,"ShelfLocCode":"387155","RFID":null,"PaidValue":null,"Medium":"Server","Description":"VLIZ Open Access","Acronym":"VLIZ","Library":"Vlaams Instituut voor de Zee","DutchTerm":"Open access","URL":null,"ClassifID":53,"Classification":"Open access","ReqLink":null,"ClassifTypID":1,"URLLocation":"https://www.vliz.be/imisdocs/publications/","SubDir":null,"InternalReq":0,"LoggedInReq":0,"Disclaimer":null,"DutchDisclaimer":null,"FileFormat":".pdf","FileDescr":"pdf","InsPub":1,"InsID":36,"FileFormID":6,"LendableFlag":1,"PublicFlag":1,"orderLib":"A","Notes":null,"AccConID":null,"AccessConstraint":null,"LicURL":null}],"litstyles":null,"thespers":null,"arch2discl":null,"SERpubls":[{"PublName":"MDPI AG","City":"Basel"}],"MONpubls":null,"pictures":[],"thestermsPath":null,"thestermsASFA":null,"taxtermsASFA":[{"TaxTerm":"Conus obscurus"}],"geotermsASFA":null,"collections":[{"Collection":"OMA - Open Marien Archief","ShortName":"OMA"}],"conf":null,"proj":null,"Physdatasets":null,"spcols":{"222":{"SpName":"BMB - Belgische Mariene Bibliografie","SpColID":222,"ParSpColID":null,"TopParID":null,"ShortName":"BMB","URLLocation":null,"LibID":36,"OpenRepoFlag":null,"SpTypID":null,"TopParIDNotWebsite":null,"SpColPath":"BMB"},"221":{"SpName":"OMA - Open Marien Archief","SpColID":221,"ParSpColID":null,"TopParID":null,"ShortName":"OMA","URLLocation":null,"LibID":36,"OpenRepoFlag":1,"SpTypID":null,"TopParIDNotWebsite":null,"SpColPath":"OMA"}},"doi":null,"publs":null,"serparttypes":null,"monauthors":null,"MParts":null,"SParts":null,"hLibs":null,"langs":[{"BEntID":359279,"AbstractFlag":0,"LangID":15,"LangCode":"en","Lang":"English","DutchTerm":"Engels","LangCodeExtended":"eng"},{"BEntID":359279,"AbstractFlag":1,"LangID":15,"LangCode":"en","Lang":"English","DutchTerm":"Engels","LangCodeExtended":"eng"}],"urls":[{"URL":"https://dx.doi.org/10.3390/ijms232012096","externalID":"10.3390/ijms232012096","URLTypeCode":"DOI","URLID":113452,"URLTypID":13,"URLType":"DOI","URLPrefix":"http://dx.doi.org/"}],"thesterms":null,"taxterms":[{"TaxTerm":"Conus obscurus","AphiaID":215476,"TaxtID":53867}],"geoterms":null,"othterms":null,"asfacodes":null,"asfa2codes":null,"thestermsFRIS":null,"taxtermsFRIS":[{"TaxTerm":"Conus obscurus","DutchTerm":null,"AphiaID":215476,"TaxtID":53867}],"geotermsFRIS":null,"othtermsFRIS":null,"resmessage":"","complete":1,"sessions":{"newSesName":"Bouchti, Zohra, Z.","newSesDate":{"date":"2023-02-27 12:47:01.750000","timezone_type":3,"timezone":"Europe/Brussels"},"updSesName":"Bouchti, Zohra, Z.","updSesDate":{"date":"2023-02-27 12:47:01.750000","timezone_type":3,"timezone":"Europe/Brussels"}}}