Adenine flips out: A combination of X‐ray crystallography, 2‐aminopurine fluorescence labeling, and the use of aminoglycosides as ligands is exploited to demonstrate conformational transitions in the RNA domain that ensures accurate protein synthesis (see picture). The triggering of a conformational change of an adenine unit in the RNA by ligand binding can be used as the basis of a screening method to discover antibiotics.
Adenin dreht sich raus: Röntgenkristallographie, Fluoreszenzmarkierung mit 2‐Aminopurin und die Verwendung von Aminoglycosiden als Liganden ermöglichten den Nachweis von Konformationsänderungen an der RNA‐Domäne, die die richtige Proteinsynthese sicherstellt (siehe Bild). Das Auslösen einer Änderung der Konformation einer RNA‐Adenineinheit durch die Bindung von Liganden kann als Grundlage für eine Methode zur Suche nach Antibiotika dienen.
Two scaffolds, one target: The bacterial ribosomal decoding site is the target for natural aminoglycoside antibiotics, which bind to an internal RNA loop and thereby interfere with translation fidelity. Synthetic aminoglycoside mimetics are thought to display similar antibiotic activity while avoiding established bacterial resistance mechanisms. We describe two complementary approaches towards novel aminoglycoside mimetics that recognize the decoding‐site RNA and inhibit bacterial translation. In the first study, elements of both rational structure‐based design and diversity‐driven exploration were used to synthesize flexible acyclic mimetics (I a,b) of 2‐deoxystreptamine. The second paper outlines the accurate replacement of the 2‐deoxystreptamine pharmacophore by stereochemically defined aminomethyl–piperidine scaffolds (II a,b).
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