4′-O-substitutions determine selectivity of aminoglycoside antibiotics

  title={4′-O-substitutions determine selectivity of aminoglycoside antibiotics},
  author={D{\'e}borah Perez-Fernandez and Dmitri Shcherbakov and Tanja Matt and Ng Chyan Leong and Iwona Kudyba and Stefan Duscha and Heithem Boukari and Rashmi Patak and Srinivas Reddy Dubbaka and Kathrin Lang and Martin Meyer and Rashid Akbergenov and Pietro Freihofer and Swapna Vaddi and Pia Thommes and V Ramakrishnan and Andrea T Vasella and Erik Christian B{\"o}ttger},
  booktitle={Nature communications},
Clinical use of 2-deoxystreptamine aminoglycoside antibiotics, which target the bacterial ribosome, is compromised by adverse effects related to limited drug selectivity. Here we present a series of 4',6'-O-acetal and 4'-O-ether modifications on glucopyranosyl ring I of aminoglycosides. Chemical modifications were guided by measuring interactions between the compounds synthesized and ribosomes harbouring single point mutations in the drug-binding site, resulting in aminoglycosides that interact… CONTINUE READING