6533b870fe1ef96bd12d050b
RESEARCH PRODUCT
Targeting Nonsense: Optimization of 1,2,4-Oxadiazole TRIDs to Rescue CFTR Expression and Functionality in Cystic Fibrosis Cell Model Systems
Ivana PibiriAndrea PaceLaura LentiniMarco TutoneRaffaella MelfiAldo Di Leonardosubject
0301 basic medicineYellow fluorescent proteinCystic Fibrosisnonsense mutationCystic Fibrosis Transmembrane Conductance RegulatorCystic fibrosislcsh:Chemistry0302 clinical medicinelcsh:QH301-705.5SpectroscopyCells CulturedbiologyChemistryGeneral MedicineSmall moleculeCystic fibrosis transmembrane conductance regulatorComputer Science ApplicationsCell biologyCodon Nonsense030220 oncology & carcinogenesisNonsense mutationContext (language use)Settore BIO/11 - Biologia MolecolareCatalysisArticleInorganic Chemistry03 medical and health sciencesmedicineHumansRNA MessengerPhysical and Theoretical ChemistryMolecular BiologyGeneMessenger RNAOrganic ChemistryoxadiazolesSettore CHIM/06 - Chimica Organicapremature termination codonmedicine.diseaseSettore CHIM/08 - Chimica FarmaceuticaSettore BIO/18 - Genetica030104 developmental biologyGene Expression Regulationlcsh:Biology (General)lcsh:QD1-999translational readthrough inducing drugsProtein BiosynthesisMutationbiology.proteingenetic disorderdescription
Cystic fibrosis (CF) patients develop a severe form of the disease when the cystic fibrosis transmembrane conductance regulator (CFTR) gene is affected by nonsense mutations. Nonsense mutations are responsible for the presence of a premature termination codon (PTC) in the mRNA, creating a lack of functional protein. In this context, translational readthrough-inducing drugs (TRIDs) represent a promising approach to correct the basic defect caused by PTCs. By using computational optimization and biological screening, we identified three new small molecules showing high readthrough activity. The activity of these compounds has been verified by evaluating CFTR expression and functionality after treatment with the selected molecules in cells expressing nonsense&ndash
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2020-09-03 | International Journal of Molecular Sciences |