Novel aminoglycosides and uses thereof in the treatment of genetic disorders
A new class of paromomycin-derived aminoglycosides, which exhibit efficient stop-codon mutation suppression activity, low toxicity and high selectivity towards eukaryotic cells are provided. Also provided are chemical and chemo-enzymatic processes of preparing these paromomycin-derived aminoglycosides and intermediates thereof, as well as pharmaceutical compositions containing the same, and uses thereof in the treatment of genetic disorders.
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Page/Page column 54-56
(2009/04/24)
Development of novel aminoglycoside (NB54) with reduced toxicity and enhanced suppression of disease-causing premature stop mutations
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-st
Combined chemical-enzymatic assembly of aminoglycoside derivatives with N-1-AHB side chain
A series of unprotected pseudo-disaccharides and pseudo-trisaccharides of 2-deoxystreptamine-containing aminoglycosides have been selectively acylated at the N-1 position with the valuable (S)-4-amino-2-hydroxybutanoyl (AHB) pharmacophore by using the recombinant BtrH and BtrG enzymes from butirosin biosynthesis in combination with a synthetic acyl donor. The process was optimized by performing two enzymatic steps in a sequential manner without purification of the intermediate product.
Nudelman, Igor,Chen, Lilach,Llewellyn, Nicholas M.,Sahraoui, El-Habib,Cherniavsky, Marina,Spencer, Jonathan B.,Baasova, Timor
experimental part
p. 1682 - 1688
(2009/08/12)
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