Redesign of aminoglycosides for treatment of human genetic diseases caused by premature stop mutations.
A series of new derivatives of the clinically used aminoglycoside antibiotic paromomycin were designed, synthesized, and their ability to read-through premature stop codon mutations was examined in both in vitro translation system and ex vivo mammalian cultured cells. One of these structures, a pseudo-trisaccharide derivative, showed notably higher stop codon read-through activity in cultured cells compared to those of paromomycin and gentamicin.
Nudelman
Igor
I
The Edith and Joseph Fischer Enzyme Inhibitors Laboratory, Department of Chemistry, Institute of Catalysis Science and Technology, Technion-Israel Institute of Technology, Haifa 32000, Israel.
Rebibo-Sabbah
Annie
A
Shallom-Shezifi
Dalia
D
Hainrichson
Mariana
M
Stahl
Ido
I
Ben-Yosef
Tamar
T
Baasov
Timor
T
D000617:Aminoglycosides / Q000138:chemical synthesis* / Q000737:chemistry / Q000627:therapeutic use*; D002236:Carbohydrate Conformation; D018388:Codon, Terminator / Q000235:genetics*; D015195:Drug Design; D030342:Genetic Diseases, Inborn / Q000188:drug therapy* / Q000235:genetics*; D008958:Models, Molecular; D008968:Molecular Conformation; D009154:Mutation
D000617:Aminoglycosides; D018388:Codon, Terminator