Leishmaniasis can be treated with Selective Ribosome-Targeting Drug with Low Ototoxicity

In the new study, a team of researchers, led by Timor Baasov, professor at the Technion – Israel Institute of Technology (Haifa, Israel), investigated the structural basis for the targeting of leishmanial ribosomes by AGs and performed comparative testing of the potential clinical effectiveness and side-effects of new (semi-) synthetic derivatives of aminoglycoside paromomycin (PAR). In a multidisciplinary biological study, researchers have shed new light on the mechanism of action of a potent drug for leishmaniasis, the natural aminoglycoside paromomycin (PAR), and have found that a new synthetic derivative of PAR may provide a far lower risk of irreversible hearing loss side-effects, probably via its more selective targeting of cytosolic (vs. mitochondrial) ribosomes. In the new study, the researchers present, for the first time, X-ray crystallography results of PAR bound in complex with a ribosomal RNA (rRNA) model mimicking two leishmanial cytosolic ribosomal binding sites (ribosomal “A-sites”).

Image: Surface representations of the binding sites of aminoglycosides paromomycin (PAR) (A) and G418 (B) in bacterial and leishmanial ribosomes.

Image: Surface representations of the binding sites of aminoglycosides paromomycin (PAR) (A) and G418 (B) in bacterial and leishmanial ribosomes.

 

 

 

 

 

 

 

Original link: http://www.biotechdaily.com/drug_discovery/articles/294760264/selective_ribosometargeting_drug_with_low_ototoxicity_could_provide_safer_treatment_option_for_leishmaniasis.html