Publications (3)15.69 Total impact
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Article: Development of novel aminoglycoside (NB54) with reduced toxicity and enhanced suppression of disease-causing premature stop mutations.
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ABSTRACT: Nonsense mutations promote premature translational termination and represent the underlying cause of a large number of human genetic diseases. The aminoglycoside antibiotic gentamicin has the ability to allow the mammalian ribosome to read past a false-stop signal and generate full-length functional proteins. However, severe toxic side effects along with the reduced suppression efficiency at subtoxic doses limit the use of gentamicin for suppression therapy. We describe here the first systematic development of the novel aminoglycoside 2 (NB54) exhibiting superior in vitro readthrough efficiency to that of gentamicin in seven different DNA fragments derived from mutant genes carrying nonsense mutations representing the genetic diseases Usher syndrome, cystic fibrosis, Duchenne muscular dystrophy, and Hurler syndrome. Comparative acute lethal toxicity in mice, cell toxicity, and the assessment of hair cell toxicity in cochlear explants further indicated that 2 exhibits far lower toxicity than that of gentamicin.Journal of Medicinal Chemistry 04/2009; 52(9):2836-45. · 4.80 Impact Factor -
Article: Combined Chemical‐Enzymatic Assembly of Aminoglycoside Derivatives with N‐1‐AHB Side Chain
Advanced Synthesis & Catalysis 06/2008; 350(11‐12):1682 - 1688. · 6.05 Impact Factor -
Article: Overexpression and initial characterization of the chromosomal aminoglycoside 3'-O-phosphotransferase APH(3')-IIb from Pseudomonas aeruginosa.
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ABSTRACT: The chromosomal gene aph(3')-IIb, encoding an aminoglycoside 3'-phosphotransferase in Pseudomonas aeruginosa, was cloned and overexpressed in Escherichia coli. The APH(3')-IIb enzyme was purified as a monomer in a two-step procedure and was shown to phosphorylate its substrates at the C-3'-OH position, with kcat/Km values of 0.4x10(4) to 36x10(4) M-1 s-1.Antimicrobial Agents and Chemotherapy 03/2007; 51(2):774-6. · 4.84 Impact Factor
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Institutions
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2007–2009
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Technion - Israel Institute of Technology
- Faculty of Biotechnology and Food Engineering
Haifa, Haifa District, Israel
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