C-glycosyl compounds bind to receptors on the surface of Escherichia coli and can target proteins to the organism.
A series of C-mannopyranosyl derivatives have been synthesized and their inhibitory activity towards the receptor-mediated adhesion of E. coli to yeast cells has been tested. Total inhibition of yeast-cell agglutination by C-glycosyl derivatives 4 and 9 is achieved at a concentration approximately one order of magnitude lower than that of methyl alpha-D-mannopyranoside, indicating that the binding affinity to the receptor is related to the hydrophobicity of the carbon-linked side chain. A biotin-linked C-glycosyl derivative of mannose (compound 9) has been synthesized and used to target avidin and streptavidin to the bacterial cell surface. Of the C-glycosyl derivatives tested in our study, the conjugate of compound 9 with avidin had the highest avidity for the bacterial receptors, inhibiting agglutination at a concentration three orders of magnitude lower than methyl alpha-D-mannopyranoside. The use of such bifunctional compounds as the mannose-biotin conjugate 9 is a general strategy to target molecules to pathogenic organisms via their cell-surface carbohydrate receptors and to change the antigenicity of the bacterial cell surface.
Bertozzi
C
C
Department of Chemistry, University of California, Berkeley 94720.
Bednarski
M
M
D001422:Bacterial Adhesion / Q000187:drug effects*; D004926:Escherichia coli / Q000187:drug effects / Q000502:physiology*; D007202:Indicators and Reagents; D037102:Lectins / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy; D008362:Mannosides / Q000138:chemical synthesis / Q000378:metabolism* / Q000494:pharmacology*; D009904:Optical Rotation; D012441:Saccharomyces cerevisiae; D013329:Structure-Activity Relationship
D007202:Indicators and Reagents; D037102:Lectins; D008362:Mannosides