Janek Szychowski

TL;DR: Antibacterial aminoglycosides with a modified mode of binding to the ribosomal-RNA decoding site and their application in drug discovery and development is described.

TL;DR: In this paper, a series of 2 O-substituted ether analogues of paromomycin were prepared based on new site-selective functionalizations, and X-ray cocrystal complexes of several such analogues revealed a new mode of binding in the A-site rRNA, whereby rings I and II adopted the familiar orientation and position previously observed with paromycin, but rings III and IV were oriented differently.

TL;DR: Improved antibacterial activity supports the conclusion that analogue 1 might affect protein synthesis on the ribosome in two different ways: 1) specific binding to the A site forces maintenance of the “on” state with two bulged out adenines, and 2) a new binding mode of 1 to an A‐minor motif which stabilizes complex formation between the Ribosome and the mRNA–tRNA complex regardless of whether the codon–anticodon stem is of the

TL;DR: Incorporation of an hydrophobic (phenethylamino)ethyl ether at C2″ of N1-(HABA)-3',4'-dideoxyparomomycin led to a novel analog with an excellent antibacterial profile against a host of resistant bacteria.

TL;DR: The future of these antibiotics will eventually be compromised by the emergence of bacterial resistance, and in order to overcome this threat to human health, the structures of some other classes of antibiotics have also been substantially modified.