Search results for "PTCs readthrough"

showing 2 items of 2 documents

Exploring the readthrough of nonsense mutations by non-acidic Ataluren analogues selected by ligand-based virtual screening

2016

Abstract Ataluren, also known as PTC124, is a 5-(fluorophenyl)-1,2,4-oxadiazolyl-benzoic acid suggested to suppress nonsense mutations by readthrough of premature stop codons in the mRNA. Potential interaction of PTC124 with mRNA has been recently studied by molecular dynamics simulations highlighting the importance of H-bonding and stacking π−π interactions. A series of non-acidic analogues of PTC124 were selected from a large database via a ligand-based virtual screening approach. Eight of them were synthesized and tested for their readthrough activity using the Fluc reporter harboring the UGA premature stop codon. The most active compound was further tested for suppression of the UGA non…

0301 basic medicineNonsense mutationDrug Evaluation PreclinicalMolecular ConformationCystic Fibrosis Transmembrane Conductance RegulatorMolecular Dynamics SimulationOxadiazolemedicine.disease_causeCftr geneCFTR gene03 medical and health scienceschemistry.chemical_compoundDrug DiscoverymedicineHumansRNA MessengerPharmacologyGeneticsOxadiazolesMessenger RNAVirtual screeningMutationNonsense mutationChemistryDrug Discovery3003 Pharmaceutical ScienceOrganic ChemistryGeneral MedicineLigand (biochemistry)PTCs readthroughMolecular biologyStop codonAtaluren030104 developmental biologyCodon NonsenseCystic fibrosiHeLa CellsEuropean Journal of Medicinal Chemistry
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Enhancement of premature stop codon readthrough in the CFTR gene by Ataluren (PTC124) derivatives.

2015

Abstract Premature stop codons are the result of nonsense mutations occurring within the coding sequence of a gene. These mutations lead to the synthesis of a truncated protein and are responsible for several genetic diseases. A potential pharmacological approach to treat these diseases is to promote the translational readthrough of premature stop codons by small molecules aiming to restore the full-length protein. The compound PTC124 (Ataluren) was reported to promote the readthrough of the premature UGA stop codon, although its activity was questioned. The potential interaction of PTC124 with mutated mRNA was recently suggested by molecular dynamics (MD) studies highlighting the importanc…

Cystic FibrosisNonsense mutationPeptide Chain Elongation TranslationalCystic Fibrosis Transmembrane Conductance RegulatorSettore BIO/11 - Biologia MolecolareMolecular Dynamics SimulationCFTR genechemistry.chemical_compoundStructure-Activity RelationshipPlasmidDrug DiscoveryTumor Cells CulturedCoding regionHumansGreen fluorescent proteinGenePharmacologyGeneticsMessenger RNAOxadiazolesNonsense mutationDose-Response Relationship DrugMolecular StructureDrug Discovery3003 Pharmaceutical ScienceOrganic ChemistryTranslational readthroughSettore CHIM/06 - Chimica OrganicaGeneral MedicinePTCs readthroughStop codonAtalurenSettore BIO/18 - GeneticachemistrySettore CHIM/03 - Chimica Generale E InorganicaCodon NonsenseCystic fibrosiMutationFluorinated oxadiazoleHeLa CellsEuropean journal of medicinal chemistry
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