4. | Understanding Carbohydrate-Nucleic Acid Interactions: Design of Novel Aminoglycoside Antibiotics |
The exact nature of the specific interactions of aminoglycoside antibiotics and particular RNA sequences is not completely understood. In order to dissect important binding interactions and to learn the rules that apply to these binding processes, we have begun to assemble modified aminoglycosides that allow us to systematically investigate the elements involved in carbohydrate-RNA recognition. Thus, di- and trisaccharides were assembled and screened for binding to different bacterial RNA sites using mass spectrometry (collaboration with ISIS Pharmaceuticals). After finishing a detailed analysis of the A-ring and the central deoxystreptamine core (B-ring) of neomycin compounds that exhibit much improved selectivity in RNA binding were identified. A series of novel trisaccharides are currently undergoing binding tests. |