Synthesis of PEGylated lactose analogs for inhibition studies on T.cruzi trans-sialidase

GIORGI, M.E.; RATIER, L.; AGUSTI, R.; FRASCH, A.C.C.; LEDERKREMER, R.M.

GLYCOCONJUGATE JOURNAL

SPRINGER

Lugar: New York; Año: 2010 vol. 27 p. 549 - 559

0282-0080

Trypanosoma cruzi, the agent of Chagas disease, expresses a unique enzyme, the trans-sialidase (TcTS) involved in the transfer of sialic acid from host glycoconjugates to mucins of the parasite. The enzyme is shed to the medium and may affect the immune system of the host. We have previously described that lactose derivatives effectively inhibited the transfer of sialic acid to Nacetyllactosamine. Lactitol also prevented the apoptosis caused by the TcTS, although it is rapidly eliminated from the circulatory system. In this paper we report covalent conjugation of polyethylene glycol (PEG) with lactose, lactobionolactone and benzyl β-D-galactopyranosyl-(1→6)-2-amino-2-deoxy-α-D-glucopyranoside (1) with the hope to improve the bioavailability, though retaining their inhibitory properties. Different conjugation methods have been used and the behavior of the PEGylated productsin the TcTS reaction was studied.