Probing the acceptor substrate binding site of Trypanosoma cruzi trans-sialidase with systematically modified substrates and glycoside libraries

Summary, in English

Systematically modified octyl galactosides and octyl N-acetyllactosamines were assessed as inhibitors of, and substrates for, T. cruzi trans-sialidase (TcTS) in the context of exploring its acceptor substrate binding site. These studies show that TcTS, which catalyses the alpha-(2 -> 3)-sialylation of non-reducing terminal beta-galactose residues, is largely intolerant of substitution of the galactose 2 and 4 positions whereas substitution of the galactose 6 position is well tolerated. Further studies show that even the addition of a bulky sugar residue (glucose, galactose) does not impact negatively on TcTS binding and turnover, which highlights the potential of 'internal' 6-substituted galactose residues to serve as TcTS acceptor substrates. Results from screening a 93-membered thiogalactoside library highlight a number of structural features (notably imidazoles and indoles) that are worthy of further investigation in the context of TcTS inhibitor development.

• Författare: Jennifer A. Harrison; K. P. Ravindranathan Kartha; Eric J. L. Fournier; Todd L. Lowary; Carles Malet; Ulf Nilsson; Ole Hindsgaul; Sergio Schenkman; James H. Naismith; Robert A. Field
• Avdelning/ar: Centrum för analys och syntes
• Publiceringsår: 2011
• Språk: Engelska
• Sidor: 1653-1660
• Publikation/Tidskrift/Serie: Organic and Biomolecular Chemistry
• Volym: 9
• Issue: 5
• Länkar: http://dx.doi.org/10.1039/c0ob00826e
• Dokumenttyp: Artikel i tidskrift
• Förlag: Royal Society of Chemistry
• Ämne: Organic Chemistry
• Status: Published
• ISBN/ISSN/Övrigt: ISSN: 1477-0539