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 language | English (US) |
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Article number | e00142-19 |
Journal | mSphere |
Volume | 4 |
Issue number | 3 |
DOIs | |
State | Published - May 1 2019 |
Keywords
- Chemical biology
- Click chemistry
- Glycobiology
- Intracellular pathogen
- Porcine esterase
- Small molecular delivery
- Toxoplasma gondii
ASJC Scopus subject areas
- Microbiology
- Molecular Biology