Synthesis of the O-linked hexasaccharide containing b-D-Galp-(1-2)-D-Galf in Trypanosoma cruzi mucins. Differences on sialylation by trans-sialidase of the two constituent hexasaccharides

AGUSTI, ROSALÍA; GIORGI, MARIA EUGENIA; MENDOZA, VM; KASHIWAGI, G; LEDERKREMER, RM; GALLO-RODRIGUEZ, C

BIOORGANIC & MEDICINAL CHEMISTRY.

PERGAMON-ELSEVIER SCIENCE LTD

Lugar: La Jolla, California; Año: 2015 vol. 23 p. 1213 - 1222

0968-0896

he hexasaccharide β-D-Galp-(1→2)-[β-D-Galp-(1→3)]-β-D-Galp-(1→6)-[β-D-Galp(1→2)-β-D-Galf(1→4)]-D-GlcNAc (10) and its β-D-Galf-(1→2)-β-D-Galf containing isomer (7) are the largestcarbohydrates in mucins of some strains of T. cruzi. The terminal β-D-Galp units are sites of sialylationby the parasite trans-sialidase. Hexasaccharide 10 was chemically synthesized for the first time by a[3+3] nitrilium based convergent approach, using the trichloroacetimidate method of glycosylation.The 1H NMR spectrum of its alditol was identical to the spectrum of the product released by β-elimination from the parasite mucin. The trans-sialylation reaction studied on the benzyl glycoside of10 showed two monosialylated products whose relative abundance changed with time. On the otherhand, only one product was produced by sialylation of the benzyl glycoside of 7. A preparativesynthesis of the latter and spectroscopic analysis of the product unequivocally established thesialylation site at the less hindered (1→3)-linked galactopyranose.