Bicyclic azetidines kill the diarrheal pathogen Cryptosporidium in mice by inhibiting parasite phenylalanyl-tRNA synthetase

Author:

Vinayak Sumiti1ORCID,Jumani Rajiv S.2,Miller Peter3,Hasan Muhammad M.2,McLeod Briana I.4ORCID,Tandel Jayesh4ORCID,Stebbins Erin E.3,Teixeira Jose E.3,Borrel Julien5ORCID,Gonse Arthur5,Zhang Mingliang6ORCID,Yu Xianshui6ORCID,Wernimont Amy7,Walpole Chris7,Eckley Sean8,Love Melissa S.9ORCID,McNamara Case W.9ORCID,Sharma Manmohan10,Sharma Amit10,Scherer Christina A.5,Kato Nobutaka5,Schreiber Stuart L.511ORCID,Melillo Bruno51112ORCID,Striepen Boris4ORCID,Huston Christopher D.3ORCID,Comer Eamon5ORCID

Affiliation:

1. Department of Pathobiology, College of Veterinary Medicine, University of Illinois at Urbana-Champaign, Urbana, IL 61802, USA.

2. Cellular, Molecular and Biomedical Sciences Graduate Program, University of Vermont, Burlington, VT 05405, USA.

3. Department of Medicine, Larner College of Medicine, University of Vermont, Burlington, VT 05405, USA.

4. Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.

5. Chemical Biology and Therapeutics Science Program, Broad Institute, Cambridge, MA 02142, USA.

6. International Discovery Service Unit, WuXi AppTec (Tianjin) Co. Ltd., Tianjin 300457, P.R. China.

7. Structural Genomics Consortium, MaRS Building, South Tower, 101 College Street, Suite 700, Toronto, Ontario M5G 1L7, Canada.

8. Eisai Inc., Cambridge, MA 02140, USA.

9. Calibr, a division of The Scripps Research Institute, La Jolla, CA 92037, USA.

10. Structural Parasitology, Molecular Medicine Group, International Centre for Genetic Engineering and Biotechnology, Aruna Asaf Ali Road, New Delhi 110070, India.

11. Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA 02138, USA.

12. Department of Chemistry, The Scripps Research Institute, La Jolla, CA 92037, USA.

Abstract

Bicyclic azetidines potently inhibit Cryptosporidium in vivo by targeting phenylalanyl-tRNA synthetase.

Funder

National Institute of Allergy and Infectious Diseases

Bill and Melinda Gates Foundation

Publisher

American Association for the Advancement of Science (AAAS)

Subject

General Medicine

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