The tightest non-aminoglycoside ligand for the bacterial ribosomal RNA A-site

Traditional aminoglycoside antibiotics are problematic given their high toxicity and the potential for resistance development. The research at Tohoku University focused on bacterial A-site binding small ligands whose structures are distinct from the aminoglycoside family, which offer potential for the development of novel drugs that treat bacterial infections with a reduction in the problems associated with traditional antibiotics.

The research group led by Dr. Seiichi Nishizawa and Dr. Yusuke Sato (Department of Chemistry, Graduate School of Science) has reported a novel small ligand, ATMND-C2-NH2 that has the tightest binding affinity for the bacterial A-site among the non-aminoglycoside ligands.

ATMND-C2-NH2 shows a significant fluorescent quenching response upon selective binding to the internal loop of the bacterial (Escherichia coli) A-site-containing model RNA. ATMND-C2-NH2 has also proven useful as an indicator for assessing ligand/A-site interactions.

The results obtained by the research group offer a rational basis for the generation of novel A-site binding ligands with a view toward novel antibiotics with less toxicity and minimum resistance development.

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Journal Reference:

1. Yusuke Sato, Masafumi Rokugawa, Sho Ito, Sayaka Yajima, Hiroki Sugawara, Norio Teramae, Seiichi Nishizawa. Fluorescent Trimethylated Naphthyridine Derivative with an Aminoalkyl Side Chain as the Tightest Non-aminoglycoside Ligand for the Bacterial A-site RNA. Chemistry - A European Journal, 2018; 24 (52): 13862 DOI: 10.1002/chem.201802320