Structure-based design, synthesis and A-site rRNA co-crystal complexes of novel amphiphilic aminoglycoside antibiotics with new binding modes: a synergistic hydrophobic effect against resistant bacteria.
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.
Hanessian
Stephen
S
Department of Chemistry, Université de Montréal, Montréal, Canada. stephen.hanessian@umontreal.ca
Pachamuthu
Kandasamy
K
Szychowski
Janek
J
Giguère
Alexandre
A
Swayze
Eric E
EE
Migawa
Michael T
MT
François
Boris
B
Kondo
Jiro
J
Westhof
Eric
E
D000617:Aminoglycosides / Q000737:chemistry*; D000900:Anti-Bacterial Agents / Q000737:chemistry* / Q000494:pharmacology; D001419:Bacteria / Q000187:drug effects*; D003460:Crystallization; D015195:Drug Design; D024881:Drug Resistance, Bacterial; D057927:Hydrophobic and Hydrophilic Interactions; D012335:RNA, Ribosomal / Q000737:chemistry*
D000617:Aminoglycosides; D000900:Anti-Bacterial Agents; D012335:RNA, Ribosomal