Disaccharide mimetics of the aminoglycoside antibiotic neamine.
A highly convergent approach has been employed for the facile synthesis of a library of 24 disaccharides that are alpha(1-3), beta(1-3), alpha(1-4), or beta(1-4) linked and contain 2-4 amino groups. Fourier-transformation ion cyclotron resonance mass spectrometry (FT-ICR MS) has been used to determine dissociation constant (Kd) values for the binding of the disaccharides to a prototypical fragment of 16S ribosomal RNA. Several derivatives bound with affinities similar to that of neamine. Structure-activity relationships have revealed the substitution pattern that is important for high-affinity binding. The compounds described here are unique lead compounds for the design of novel aminoglycoside antibiotics.
Venot
Andre
A
Complex Carbohydrate Research Center, University of Georgia, 315 Riverbend Road, Athens, GA 30602, USA.
Swayze
Eric E
EE
Griffey
Richard H
RH
Boons
Geert-Jan
GJ
D000617:Aminoglycosides / Q000737:chemistry*; D002240:Carbohydrate Sequence; D018360:Crystallography, X-Ray; D004187:Disaccharides / Q000138:chemical synthesis / Q000737:chemistry*; D005601:Framycetin; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D008968:Molecular Conformation; D008969:Molecular Sequence Data; D012313:RNA / Q000096:biosynthesis / Q000235:genetics; D013329:Structure-Activity Relationship
D000617:Aminoglycosides; D004187:Disaccharides; D005601:Framycetin; C488396:neamine; D012313:RNA