Potent fluoro-oligosaccharide probes of adhesion in Toxoplasmosis.
Unnatural, NMR- and MRI-active fluorinated sugar probes, designed and synthesised to bind to the pathogenic protein TgMIC1 from Toxoplasma gondii, were found to display binding potency equal to and above that of the natural ligand. Dissection of the binding mechanism and modes, including the first X-ray crystal structures of a fluoro-oligosaccharide bound to a lectin, demonstrate that it is possible to create effective fluorinated probe ligands for the study of, and perhaps intervention in, sugar-protein binding events.
Allman
Sarah A
SA
Department of Chemistry, University of Oxford, Chemistry Research Laboratory, Mansfield Road, Oxford OX13TA, UK.
Jensen
Henrik H
HH
Vijayakrishnan
Balakumar
B
Garnett
James A
JA
Leon
Ester
E
Liu
Yan
Y
Anthony
Daniel C
DC
Sibson
Nicola R
NR
Feizi
Ten
T
Matthews
Stephen
S
Davis
Benjamin G
BG
D050260:Carbohydrate Metabolism; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000737:chemistry / Q000378:metabolism; D018360:Crystallography, X-Ray; D004187:Disaccharides / Q000138:chemical synthesis / Q000737:chemistry; D054879:Halogenation; D015335:Molecular Probes / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism*; D009844:Oligosaccharides / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism*; D015800:Protozoan Proteins / Q000737:chemistry / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000378:metabolism; D014122:Toxoplasma / Q000166:cytology* / Q000378:metabolism; D014123:Toxoplasmosis / Q000469:parasitology*
D015815:Cell Adhesion Molecules; D004187:Disaccharides; C105877:MIC1 protein, Toxoplasma gondii; D015335:Molecular Probes; D009844:Oligosaccharides; D015800:Protozoan Proteins; D011956:Receptors, Cell Surface; C055213:saccharide-binding proteins