Trypanosoma cruzi trans-sialidase, substrates and inhibitors

MUCHNIK DE LEDERKREMER, ROSA

New Orleans

Conferencia; Sugar Alley Symposium; 2008

American Chemical Society

The trans-sialidase from Trypanosoma cruzi (TcTS), the agent of Chagasf disease, is a unique enzyme important for the survival of the parasite in the mammalian or insect host. This process involves the transfer of a-(2¨3)-linked sialic acid from host glycoconjugates to terminal b-galactopyranosyl units of parasite mucins. This is the pathway that T. cruzi utilizes to incorporate sialic acid. The O-chains, in the acceptors, may be derived from two cores, Galp(b1¨4)GlcNAc or Galf(b¨4)GlcNAc. The cores are further branched with various units of Galf and/or Galp. The presence of Galf is related to the lineage of the T. cruzi strain. In our laboratory we have undertaken the chemical synthesis of the Galf-containing oligosaccharides in order to correlate their structure with the ability to act as substrates of the TcTS.  Also, compounds directed to the lactose binding site of TcTS were evaluated as inhibitors for the sialylation of N-acetyllactosamine.