Loop conformation: The loop of the RNA domain helix 69 (H69) was modified with the fluorescent analogue 2‐aminopurine (2AP), thus showing different conformational states under various conditions. The application of this model RNA reveals the unique impact of aminoglycoside neomycin, which differs from the effects of structurally related compounds paromomycin and gentamicin, on the H69 loop conformation in solution (see picture).

Antibiotic resistance prevents successful treatment of common bacterial infections, making it clear that new target locations and drugs are required to resolve this ongoing challenge. The bacterial ribosome is a common target for antibacterials due to its essential contribution to cell viability. The focus of this work is a region of the ribosome called helix 69 (H69), which was recently identified as a secondary target site for aminoglycoside antibiotics. H69 has key roles in essential ribosomal processes such as subunit association, ribosome recycling, and tRNA selection. Conserved across phylogeny, bacterial H69 also contains two pseudouridines and one 3-methylpseudouridine. Phage display revealed a heptameric peptide sequence that targeted H69. Using solid-phase synthesis, peptide variants with higher affinity and improved selectivity to modified H69 were generated. Electrospray ionization mass spectrometry was used to determine relative apparent dissociation constants of the RNA-peptide complexes.

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Schleifenkonformation: Die Schleife der RNA‐Domäne Helix‐69 (H69) wurde mit dem fluoreszierenden Adenin‐Analogon 2‐Aminopurin (2AP) modifiziert, was die je nach den Bedingungen unterschiedlichen Konformationszustände sichtbar machte. Die Verwendung dieser Modell‐RNA zeigt den besonderen Einfluss des Aminoglycosids Neomycin auf die Schleifenkonformation von H69, der sich von dem der strukturell ähnlichen Verbindungen Paromomycin und Gentamicin unterscheidet (siehe Bild).