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Antibiotics: where to throw the spanner in the ribosomal machinery?
Future Medicinal Chemistry 2016 September 22
The sheer molecular scale of the ribosome is intimidating to the traditional drug designer. By analyzing the ribosome as a series of 12 key target sites, this review seeks to make the ribosome ligand design process more manageable. Analysis of recently evaluated ribosomal structures, particularly those with bound antibiotics, indicates where the ligand target sites are located. This review employs current research data to map antibiotic binding across the ribosome. A number of neighboring ligand-binding sites are often contiguous and can be combined. Ligands that bind in close proximity can be combined into hybrid structures. The different ways antibiotics disrupt ribosomal function are also discussed. Antibiotics tend to inhibit conformational changes that are essential to the ribosomal mechanism.
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