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Aryl amino acetamid...
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Dans, Madeline G.Burnet Institute, VIC, Melbourne, Australia; Walter and Eliza Hall Institute, VIC, Parkville, Australia; Institute of Mental and Physical Health and Clinical Translation (IMPACT) and School of Medicine, Deakin University, VIC, Geelong, Australia; Department of Medical Biology, The University of Melbourne, VIC, Parkville, Australia
(författare)
Aryl amino acetamides prevent Plasmodium falciparum ring development via targeting the lipid-transfer protein PfSTART1
- Artikel/kapitelEngelska2024
Förlag, utgivningsår, omfång ...
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Springer Nature,2024
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electronicrdacarrier
Nummerbeteckningar
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LIBRIS-ID:oai:DiVA.org:umu-227301
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https://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-227301URI
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https://doi.org/10.1038/s41467-024-49491-8DOI
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Språk:engelska
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Sammanfattning på:engelska
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Ämneskategori:ref swepub-contenttype
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Ämneskategori:art swepub-publicationtype
Anmärkningar
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With resistance to most antimalarials increasing, it is imperative that new drugs are developed. We previously identified an aryl acetamide compound, MMV006833 (M-833), that inhibited the ring-stage development of newly invaded merozoites. Here, we select parasites resistant to M-833 and identify mutations in the START lipid transfer protein (PF3D7_0104200, PfSTART1). Introducing PfSTART1 mutations into wildtype parasites reproduces resistance to M-833 as well as to more potent analogues. PfSTART1 binding to the analogues is validated using organic solvent-based Proteome Integral Solubility Alteration (Solvent PISA) assays. Imaging of invading merozoites shows the inhibitors prevent the development of ring-stage parasites potentially by inhibiting the expansion of the encasing parasitophorous vacuole membrane. The PfSTART1-targeting compounds also block transmission to mosquitoes and with multiple stages of the parasite’s lifecycle being affected, PfSTART1 represents a drug target with a new mechanism of action.
Ämnesord och genrebeteckningar
Biuppslag (personer, institutioner, konferenser, titlar ...)
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Boulet, CoralieBurnet Institute, VIC, Melbourne, Australia; Department of Microbiology and Molecular Medicine, University of Geneva, Geneva, Switzerland
(författare)
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Watson, Gabrielle M.Walter and Eliza Hall Institute, VIC, Parkville, Australia; Department of Medical Biology, The University of Melbourne, VIC, Parkville, Australia
(författare)
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Nguyen, WilliamWalter and Eliza Hall Institute, VIC, Parkville, Australia; Department of Medical Biology, The University of Melbourne, VIC, Parkville, Australia
(författare)
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Dziekan, Jerzy M.Walter and Eliza Hall Institute, VIC, Parkville, Australia; Department of Medical Biology, The University of Melbourne, VIC, Parkville, Australia
(författare)
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Evelyn, CindyWalter and Eliza Hall Institute, VIC, Parkville, Australia; Department of Medical Biology, The University of Melbourne, VIC, Parkville, Australia
(författare)
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Reaksudsan, KitsanapongWalter and Eliza Hall Institute, VIC, Parkville, Australia; Department of Medical Biology, The University of Melbourne, VIC, Parkville, Australia
(författare)
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Mehra, SomyaBurnet Institute, VIC, Melbourne, Australia; Institute of Mental and Physical Health and Clinical Translation (IMPACT) and School of Medicine, Deakin University, VIC, Geelong, Australia
(författare)
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Razook, ZahraBurnet Institute, VIC, Melbourne, Australia; Institute of Mental and Physical Health and Clinical Translation (IMPACT) and School of Medicine, Deakin University, VIC, Geelong, Australia
(författare)
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Geoghegan, Niall D.Walter and Eliza Hall Institute, VIC, Parkville, Australia; Department of Medical Biology, The University of Melbourne, VIC, Parkville, Australia
(författare)
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Mlodzianoski, Michael J.Walter and Eliza Hall Institute, VIC, Parkville, Australia; Department of Medical Biology, The University of Melbourne, VIC, Parkville, Australia
(författare)
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Goodman, Christopher DeanSchool of Biosciences, The University of Melbourne, VIC, Parkville, Australia
(författare)
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Ling, Dawson B.Burnet Institute, VIC, Melbourne, Australia
(författare)
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Jonsdottir, Thorey K.Umeå universitet,Institutionen för molekylärbiologi (Medicinska fakulteten),Burnet Institute, VIC, Melbourne, Australia; Department of Microbiology and Immunology, The University of Melbourne, VIC, Parkville, Australia; The Laboratory for Molecular Infection Medicine Sweden (MIMS), Umeå, Sweden(Swepub:umu)thjo0151
(författare)
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Tong, JoshuaWalter and Eliza Hall Institute, VIC, Parkville, Australia
(författare)
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Famodimu, Mufuliat ToyinDepartment of Infection Biology, Faculty of Infectious Diseases, London School of Hygiene and Tropical Medicine, London, United Kingdom
(författare)
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Kristan, MojcaWellcome Trust Human Malaria Transmission Facility, Faculty of Infectious & amp; Tropical Diseases, London School of Hygiene & amp; Tropical Medicine, London, United Kingdom
(författare)
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Pollard, HarryWellcome Trust Human Malaria Transmission Facility, Faculty of Infectious & amp; Tropical Diseases, London School of Hygiene & amp; Tropical Medicine, London, United Kingdom
(författare)
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Stewart, Lindsay B.Wellcome Trust Human Malaria Transmission Facility, Faculty of Infectious & amp; Tropical Diseases, London School of Hygiene & amp; Tropical Medicine, London, United Kingdom
(författare)
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Brandner-Garrod, LukeWellcome Trust Human Malaria Transmission Facility, Faculty of Infectious & amp; Tropical Diseases, London School of Hygiene & amp; Tropical Medicine, London, United Kingdom
(författare)
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Sutherland, Colin J.Department of Infection Biology, Faculty of Infectious Diseases, London School of Hygiene and Tropical Medicine, London, United Kingdom; Wellcome Trust Human Malaria Transmission Facility, Faculty of Infectious & amp; Tropical Diseases, London School of Hygiene & amp; Tropical Medicine, London, United Kingdom
(författare)
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Delves, Michael J.Department of Infection Biology, Faculty of Infectious Diseases, London School of Hygiene and Tropical Medicine, London, United Kingdom
(författare)
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McFadden, Geoffrey I.School of Biosciences, The University of Melbourne, VIC, Parkville, Australia
(författare)
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Barry, Alyssa E.Burnet Institute, VIC, Melbourne, Australia; Institute of Mental and Physical Health and Clinical Translation (IMPACT) and School of Medicine, Deakin University, VIC, Geelong, Australia
(författare)
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Crabb, Brendan S.Burnet Institute, VIC, Melbourne, Australia; Department of Microbiology and Immunology, The University of Melbourne, VIC, Parkville, Australia; Monash University, VIC, Melbourne, Australia
(författare)
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de Koning-Ward, Tania F.Institute of Mental and Physical Health and Clinical Translation (IMPACT) and School of Medicine, Deakin University, VIC, Geelong, Australia
(författare)
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Rogers, Kelly L.Walter and Eliza Hall Institute, VIC, Parkville, Australia; Department of Medical Biology, The University of Melbourne, VIC, Parkville, Australia
(författare)
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Cowman, Alan F.Walter and Eliza Hall Institute, VIC, Parkville, Australia; Department of Medical Biology, The University of Melbourne, VIC, Parkville, Australia
(författare)
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Tham, Wai-HongWalter and Eliza Hall Institute, VIC, Parkville, Australia; Department of Medical Biology, The University of Melbourne, VIC, Parkville, Australia
(författare)
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Sleebs, Brad E.Walter and Eliza Hall Institute, VIC, Parkville, Australia; Department of Medical Biology, The University of Melbourne, VIC, Parkville, Australia
(författare)
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Gilson, Paul R.Burnet Institute, VIC, Melbourne, Australia; Department of Microbiology and Immunology, The University of Melbourne, VIC, Parkville, Australia
(författare)
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Burnet Institute, VIC, Melbourne, Australia; Walter and Eliza Hall Institute, VIC, Parkville, Australia; Institute of Mental and Physical Health and Clinical Translation (IMPACT) and School of Medicine, Deakin University, VIC, Geelong, Australia; Department of Medical Biology, The University of Melbourne, VIC, Parkville, AustraliaBurnet Institute, VIC, Melbourne, Australia; Department of Microbiology and Molecular Medicine, University of Geneva, Geneva, Switzerland
(creator_code:org_t)
Sammanhörande titlar
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Ingår i:Nature Communications: Springer Nature15:12041-1723
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Till lärosätets databas
- Av författaren/redakt...
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Dans, Madeline G ...
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Boulet, Coralie
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Watson, Gabriell ...
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Nguyen, William
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Dziekan, Jerzy M ...
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Evelyn, Cindy
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visa fler...
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Reaksudsan, Kits ...
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Mehra, Somya
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Razook, Zahra
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Geoghegan, Niall ...
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Mlodzianoski, Mi ...
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Goodman, Christo ...
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Ling, Dawson B.
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Jonsdottir, Thor ...
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Tong, Joshua
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Famodimu, Mufuli ...
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Kristan, Mojca
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Pollard, Harry
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Stewart, Lindsay ...
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Brandner-Garrod, ...
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Sutherland, Coli ...
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Delves, Michael ...
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McFadden, Geoffr ...
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Barry, Alyssa E.
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Crabb, Brendan S ...
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de Koning-Ward, ...
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Rogers, Kelly L.
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Cowman, Alan F.
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Tham, Wai-Hong
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Sleebs, Brad E.
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Gilson, Paul R.
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