Synthesis of divalent ligands of β-thio- and β-N-galactopyranosides and related lactosides and their evaluation as substrates and inhibitors of Trypanosoma cruzi trans-sialidase

• María Emilia Cano,
• Rosalía Agusti,
• Alejandro J. Cagnoni,
• María Florencia Tesoriero,
• José Kovensky,
• María Laura Uhrig and
• Rosa M. de Lederkremer

Beilstein J. Org. Chem. 2014, 10, 3073–3086, doi:10.3762/bjoc.10.324

• . Keywords: β-galactopyranosides; multivalent ligands; sialic acid; sugar scaffolds; T. cruzi trans-sialidase; Introduction Trypanosoma cruzi, the agent of American trypanosomiasis, affects millions of people in Latin America [1][2] and is transmitted to animals, including humans, by triatomine insects. The

• -sialic acid [10]. Although TcTS can be considered as “promiscuous” with respect to the sialyl donor and the β-galactopyranoside acceptor, it should be noted that the reaction is in fact specific in vivo. Only sialic acid-linked α(2→3) to β-galactopyranosides in glycoconjugates is transferred to terminal

• binding site or to the galactose acceptor site. Inhibitors of TcTS binding to the βGalp acceptor site would be highly selective, as other sialidases lack this interaction. In this direction, a group of octyl β-galactopyranosides and octyl N-acetyllactosaminides were described as substrates as well as