Nature Communications (Aug 2022)
Elucidating the path to Plasmodium prolyl-tRNA synthetase inhibitors that overcome halofuginone resistance
- Mark A. Tye,
- N. Connor Payne,
- Catrine Johansson,
- Kritika Singh,
- Sofia A. Santos,
- Lọla Fagbami,
- Akansha Pant,
- Kayla Sylvester,
- Madeline R. Luth,
- Sofia Marques,
- Malcolm Whitman,
- Maria M. Mota,
- Elizabeth A. Winzeler,
- Amanda K. Lukens,
- Emily R. Derbyshire,
- Udo Oppermann,
- Dyann F. Wirth,
- Ralph Mazitschek
Affiliations
- Mark A. Tye
- Center for Systems Biology, Massachusetts General Hospital
- N. Connor Payne
- Center for Systems Biology, Massachusetts General Hospital
- Catrine Johansson
- Botnar Research Centre, NIHR Oxford Biomedical Research Unit, University of Oxford
- Kritika Singh
- Center for Systems Biology, Massachusetts General Hospital
- Sofia A. Santos
- Center for Systems Biology, Massachusetts General Hospital
- Lọla Fagbami
- Center for Systems Biology, Massachusetts General Hospital
- Akansha Pant
- Harvard T.H. Chan School of Public Health
- Kayla Sylvester
- Department of Chemistry, Duke University
- Madeline R. Luth
- Department of Pediatrics, University of California, San Diego
- Sofia Marques
- Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa
- Malcolm Whitman
- Department of Developmental Biology, Harvard School of Dental Medicine
- Maria M. Mota
- Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa
- Elizabeth A. Winzeler
- Department of Pediatrics, University of California, San Diego
- Amanda K. Lukens
- Broad Institute of MIT and Harvard
- Emily R. Derbyshire
- Department of Chemistry, Duke University
- Udo Oppermann
- Botnar Research Centre, NIHR Oxford Biomedical Research Unit, University of Oxford
- Dyann F. Wirth
- Harvard T.H. Chan School of Public Health
- Ralph Mazitschek
- Center for Systems Biology, Massachusetts General Hospital
- DOI
- https://doi.org/10.1038/s41467-022-32630-4
- Journal volume & issue
-
Vol. 13,
no. 1
pp. 1 – 17
Abstract
The development of antimalarials against the human liver and asexual blood stages is one of the top public health challenges. Here, the authors report a single-step biochemical assay for the characterization of prolyl-tRNA synthetase inhibitors, and develop high-affinity inhibitors for the enzyme, including elusive triple-site ligands.
