Mosquito-Derived Anophelin Sulfoproteins Are Potent Antithrombotics

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dc.contributor.authorWatson, Emma E
dc.contributor.authorLiu, Xuyu
dc.contributor.authorThompson, Robert E
dc.contributor.authorRipoll-Rozada, Jorge
dc.contributor.authorWu, Mike
dc.contributor.authorAlwis, Imala
dc.contributor.authorGori, Alessandro
dc.contributor.authorLoh, Choy
dc.contributor.authorParker, Benjamin
dc.contributor.authorOtting, Gottfried
dc.contributor.authorJackson, Shaun
dc.contributor.authorPereira, Pedro JoseĢ Barbosa
dc.date.accessioned2021-11-17T00:37:56Z
dc.date.available2021-11-17T00:37:56Z
dc.date.issued2018
dc.date.updated2020-11-23T11:48:32Z
dc.description.abstractThe anophelins are small protein thrombin inhibitors that are produced in the salivary glands of the Anopheles mosquito to fulfill a vital role in blood feeding. A bioinformatic analysis of anophelin sequences revealed the presence of conserved tyrosine residues in an acidic environment that were predicted to be post-translationally sulfated in vivo. To test this prediction, insect cell expression of two anophelin proteins, from Anopheles albimanus and Anopheles gambiae, was performed, followed by analysis by mass spectrometry, which showed heterogeneous sulfation at the predicted sites. Homogeneously sulfated variants of the two proteins were subsequently generated by chemical synthesis via a one-pot ligation-desulfurization strategy. Tyrosine sulfation of the anophelins was shown to significantly enhance the thrombin inhibitory activity, with a doubly sulfated variant of the anophelin from A. albimanus exhibiting a 100-fold increase in potency compared with the unmodified homologue. Sulfated anophelins were also shown to exhibit potent in vivo anticoagulant and antithrombotic activity.en_AU
dc.description.sponsorshipThe authors acknowledge the John A. Lamberton Research Scholarship and Australian Postgraduate Award for Ph.D. funding (E.E.W., X.L., and R.E.T.) and The National Health and Medical Research Council of Australia (Project Grant 1120941) and the Australian Research Council (FT130100150 to R.J.P and DP150100383 to G.O) for funding.en_AU
dc.format.mimetypeapplication/pdfen_AU
dc.identifier.issn2374-7951en_AU
dc.identifier.urihttp://hdl.handle.net/1885/251862
dc.language.isoen_AUen_AU
dc.provenanceThis is an open access article published under an ACS AuthorChoice License, which permits copying and redistribution of the article or any adaptations for non-commercial purposes.en_AU
dc.publisherAmerican Chemical Societyen_AU
dc.relationhttp://purl.org/au-research/grants/nhmrc/1120941en_AU
dc.relationhttp://purl.org/au-research/grants/arc/FT130100150en_AU
dc.relationhttp://purl.org/au-research/grants/arc/DP150100383en_AU
dc.rightsĀ© 2018 American Chemical Societyen_AU
dc.rights.licenseACS AuthorChoice Licenseen_AU
dc.rights.urihttps://pubs.acs.org/page/policy/authorchoice_termsofuse.htmlen_AU
dc.sourceACS Central Scienceen_AU
dc.titleMosquito-Derived Anophelin Sulfoproteins Are Potent Antithromboticsen_AU
dc.typeJournal articleen_AU
dcterms.accessRightsOpen Accessen_AU
local.bibliographicCitation.issue4en_AU
local.bibliographicCitation.lastpage476en_AU
local.bibliographicCitation.startpage468en_AU
local.contributor.affiliationWatson, Emma E, University of Sydneyen_AU
local.contributor.affiliationLiu, Xuyu, University of Sydneyen_AU
local.contributor.affiliationThompson, Robert E, University of Sydneyen_AU
local.contributor.affiliationRipoll-Rozada, Jorge, Universidade do Portoen_AU
local.contributor.affiliationWu, Mike, University of Sydneyen_AU
local.contributor.affiliationAlwis, Imala, University of Sydneyen_AU
local.contributor.affiliationGori, Alessandro, University of Sydneyen_AU
local.contributor.affiliationLoh, Choy, College of Science, ANUen_AU
local.contributor.affiliationParker, Benjamin, The University of Sydneyen_AU
local.contributor.affiliationOtting, Gottfried, College of Science, ANUen_AU
local.contributor.affiliationJackson, Shaun, University of Sydneyen_AU
local.contributor.affiliationPereira, Pedro JoseĢ Barbosa, Universidade do Portoen_AU
local.contributor.authoremailu4046684@anu.edu.auen_AU
local.contributor.authoruidLoh, Choy, u4595334en_AU
local.contributor.authoruidOtting, Gottfried, u4046684en_AU
local.description.notesImported from ARIESen_AU
local.identifier.absfor030406 - Proteins and Peptidesen_AU
local.identifier.ariespublicationa383154xPUB9799en_AU
local.identifier.citationvolume4en_AU
local.identifier.doi10.1021/acscentsci.7b00612en_AU
local.identifier.scopusID2-s2.0-85045964682
local.identifier.uidSubmittedBya383154en_AU
local.publisher.urlhttps://pubs.acs.org/en_AU
local.type.statusPublished Versionen_AU

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