Disaccharide Mimetics of the Aminoglycoside Antibiotic Neamine

• Published in: Chembiochem : a European journal of chemical biology Vol. 5; no. 9; pp. 1228 - 1236
• Main Authors: Venot, Andre, Swayze, Eric E, Griffey, Richard H, Boons, Geert-Jan
• Format: Journal Article
• Language: English
• Published: Weinheim Wiley-VCH Verlag 06-09-2004; WILEY-VCH Verlag; WILEY‐VCH Verlag
• Subjects: aminoglycosides; Aminoglycosides - chemistry; antibiotics; Carbohydrate Sequence; Crystallography, X-Ray; Disaccharides - chemical synthesis; Disaccharides - chemistry; Framycetin; glycosylations; Magnetic Resonance Spectroscopy; Models, Molecular; Molecular Conformation; Molecular Sequence Data; RNA; RNA - biosynthesis; RNA - genetics; Structure-Activity Relationship; substituent effects
• ISSN: 1439-4227; 1439-7633
• DOI: 10.1002/cbic.200400105

A highly convergent approach has been employed for the facile synthesis of a library of 24 disaccharides that are α(1-3), β(1-3), α(1-4), or β(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.