Trisaccharide mimetics of the aminoglycoside antibiotic neomycin.
A highly convergent approach for the chemical synthesis of eight structurally related trisaccharides that contain 3 to 5 amino groups has been described. Fourier-transformation ion cyclotron resonance mass spectrometry (FT-ICR MS) has been employed to determine the dissociation constants (Kd) for the binding of the trisaccharides to a prototypical fragment of 16S ribosomal RNA. A compound that contained a 4,6-dideoxy-4-amino-beta-D-glucopyranoside moiety at C-3 displayed binding in the low micromolar range. It was found that small structural changes of the saccharides resulted in large differences in affinity. The described structure-activity relationship is expected to be valuable for the development of novel antibiotics that target rRNA.
Complex Carbohydrate Research Center, University of Georgia, 315 Riverbend Road, Athens, GA 30602, USA.
Yu
Y
Rao
Andre
A
Venot
Eric E
EE
Swayze
Richard H
RH
Griffey
Geert-Jan
GJ
Boons
D002236:Carbohydrate Conformation; D002240:Carbohydrate Sequence; D005601:Framycetin / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D008958:Models, Molecular; D009355:Neomycin / Q000031:analogs & derivatives* / Q000737:chemistry*; D012313:RNA / Q000737:chemistry; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D014312:Trisaccharides / Q000138:chemical synthesis / Q000737:chemistry*
D014312:Trisaccharides; D005601:Framycetin; D012313:RNA; D009355:Neomycin