title: Donor substrate binding to trans-sialidase of Trypanosoma cruzi as studied by STD NMR.
abstract: Using STD NMR experiments, we have studied the binding epitopes of p-nitrophenyl glycosides of sialic acid and analogs thereof when bound to Trypanosoma cruzi trans-sialidase (TSia). Time-dependent NMR spectra yielded data on the rate of substrate hydrolysis in comparison to sialic acid transfer. Our experiments clearly demonstrate that shortening of the glycerol side chain significantly favors the transfer reaction over hydrolysis. Our results extend the basis on which specific trans-sialidase inhibitors may be designed.
authors.affiliation: University of Luebeck, Institute of Chemistry, Ratzeburger Allee 160, 23538 Lübeck, Germany.
authors.forename: Astrid
authors.initials: A
authors.lastname: Blume
authors.forename: Björn
authors.initials: B
authors.lastname: Neubacher
authors.forename: Joachim
authors.initials: J
authors.lastname: Thiem
authors.forename: Thomas
authors.initials: T
authors.lastname: Peters
mesh_terms: D000818:Animals; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology; D006023:Glycoproteins / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism*; D006868:Hydrolysis; D007700:Kinetics; D008024:Ligands; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D009439:Neuraminidase / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism*; D015800:Protozoan Proteins / Q000187:drug effects / Q000378:metabolism; D012794:Sialic Acids / Q000737:chemistry / Q000378:metabolism; D013379:Substrate Specificity; D014344:Trypanocidal Agents / Q000494:pharmacology*; D014349:Trypanosoma cruzi / Q000201:enzymology*
chemical_list: D004791:Enzyme Inhibitors; D006023:Glycoproteins; D008024:Ligands; D015800:Protozoan Proteins; D012794:Sialic Acids; D014344:Trypanocidal Agents; C069715:trans-sialidase; D009439:Neuraminidase