The trans-sialidase from Trypanosoma cruzi efficiently transfers alpha(2-3) linked N-glycolylneuraminic acid to terminal beta- glycosil units.

AGUSTI R; GIORGI M. E; LEDERKREMER RM

CARBOHYDRATE RESEARCH

Elsevier

Lugar: Amsterdam; Año: 2007 vol. 342 p. 2465 - 2469

0008-6215

The trans-sialidase from Trypanosoma cruzi (TcTS), the agent of Chagas´ disease, is a unique enzyme involved in mammalianhost-cell invasion. Since T. cruzi is unable to synthesize sialic acids de novo, TcTS catalyzes the transfer of a-(2-3)-sialylresidues from the glycoconjugates of the host to terminal b-galactopyranosyl units present on the surface of the parasite. TcTS alsoplays a key role in the immunomodulation of the infected host. Chronic Chagas´ disease patients elicit TcTS-neutralizing antibodiesthat are able to inhibit the enzyme. N-Glycolylneuraminic acid has been detected in T. cruzi, and the trans-sialidase was pointed outas the enzyme involved in its incorporation from host glycoconjugates. However, N-glycolylneuraminic acid a-(2-3)-linked-containingoligosaccharides have not been analyzed as donors in the T. cruzi trans-sialidase reaction. In this paper we studied the abilityof TcTS to transfer N-glycolylneuraminic acid from Neu5Gc(a2-3)Gal(b1-4)GlcbOCH2CH2N3 (1) and Neu5Gc(a2-3)Gal(b1-3)GlcNAcbOCH2CH2N3 (2) to lactitol, N-acetyllactosamine and lactose as acceptor substrates. Transfer from 1 was moreefficient (50-65%) than from 2 (20-30%) for the three acceptors. The reactions were inhibited when the enzyme was preincubatedwith a neutralizing antibody. Km values were calculated for 1 and 2 and compared with 30-sialyllactose using lactitol as acceptorsubstrate. Analysis was performed by high-performance anion-exchange (HPAEC) chromatography. A competitive transfer reactionof compound 1 in the presence of 30-sialyllactose and N-acetyllactosamine showed a better transfer of Neu5Gc than of Neu5Ac.