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.
Rao
Yu
Y
Complex Carbohydrate Research Center, University of Georgia, 315 Riverbend Road, Athens, GA 30602, USA.
Venot
Andre
A
Swayze
Eric E
EE
Griffey
Richard H
RH
Boons
Geert-Jan
GJ
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