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

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

GLYCOCONJUGATE JOURNAL

SPRINGER

Lugar: Holanda; 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 glycoconjugatesto mucins of the parasite. The enzyme is shed tothe medium and may affect the immune system of the host.We have previously described that lactose derivativeseffectively inhibited the transfer of sialic acid to Nacetyllactosamine.Lactitol also prevented the apoptosiscaused by the TcTS, although it is rapidly eliminated fromthe circulatory system. In this paper we report covalentconjugation of polyethylene glycol (PEG) with lactose,lactobionolactone and benzyl b-D-galactopyranosyl-(1-6)-2-amino-2-deoxy-a-D-glucopyranoside (1) withthe hope to improve the bioavailability, though retainingtheir inhibitory properties. Different conjugation methodshave been used and the behavior of the PEGylated productsin the TcTS reaction was studied.