Trypanosoma cruzi trans-sialidase alternative substrates: Study of the effect of substitution in C-6 in benzyl β-lactoside

MORRONE-POZZUTO, PABLO; UHRIG, MARIA LAURA; AGUSTI, ROSALIA

CARBOHYDRATE RESEARCH

ELSEVIER SCI LTD

Año: 2019 vol. 478 p. 33 - 45

0008-6215

Trypanosoma cruzi trans-sialidase (TcTS) is a cell surface protein that participates in the adhesion and invasionmechanisms of the parasite into the host cells, making it an attractive target for inhibitors design. In order tocontribute to the knowledge of the interaction between TcTS and their acceptor substrates, we designed andsynthesized a library of 20 benzyl lactosides substituted in C-6 of the glucose residue with a series of 1,2,3-triazole derivatives containing different aromatic substituents in the C-4 position. The library was prepared byalkyne-azide cycloaddition reaction catalyzed by Cu(I) (?click chemistry?) between a benzyl β-lactoside functionalizedwith an azide group in the C-6 position and a series of 2-propargyl phenyl ethers. Herein we analyzedthe chromatographic behavior on high performance anion exchange chromatography (HPAEC) of the triazoyllactosederivatives and their activity as acceptors of TcTS and inhibitors of the sialylation of N-acetyllactosamine.The triazoyl derivatives were obtained with excellent yields and all of them behaved as moderatealternative substrates. The presence of bulky hydrophobic substituents dramatically increased the retentiontimes in HPAEC but did not affect significantly their acceptor properties toward TcTS.