Stage-specific and selective delivery of caged azidosugars into the intracellular parasite Toxoplasma gondii by using an esterase-ester pair technique

Tadakimi Tomita, Hua Wang, Peng Wu, Louis M. Weissa

Research output: Contribution to journalArticle

Abstract

Toxoplasma gondii is an obligate intracellular parasite that chronically infects up to a third of the human population. The parasites persist in the form of cysts in the central nervous system and serve as a reservoir for the reactivation of toxoplasmic encephalitis. The cyst wall is known to have abundant O-linked N-acetylgalactosamine glycans, but the existing metabolic labeling methods do not allow selective labeling of intracellular parasite glycoproteins without labeling of host glycans. In this study, we have integrated Cu(I)-catalyzed bioorthogonal click chemistry with a specific esterase-ester pair system in order to selectively deliver azidosugars to the intracellular parasites. We demonstrated that α-cyclopropyl modified GalNAz was cleaved by porcine liver esterase produced in the parasites but not in the host cells. Our proof-of-concept study demonstrates the feasibility and potential of this esterase-ester click chemistry approach for the selective delivery of small molecules in a stage-specific manner.

Original languageEnglish (US)
Article numbere00142-19
JournalmSphere
Volume4
Issue number3
DOIs
StatePublished - May 1 2019

    Fingerprint

Keywords

  • Chemical biology
  • Click chemistry
  • Glycobiology
  • Intracellular pathogen
  • Porcine esterase
  • Small molecular delivery
  • Toxoplasma gondii

ASJC Scopus subject areas

  • Microbiology
  • Molecular Biology

Cite this