Strategies Against Nonsense: Oxadiazoles As Translational Readthrough-Inducing Drugs (TRIDs)

Overview

Journal Int J Mol Sci

Publisher MDPI

Specialties Biochemistry
Chemistry
Molecular Biology

Date 2019 Jul 10

PMID 31284579

Citations 23

Authors

Ambra Campofelice

Laura Lentini

Aldo Di Leonardo

Raffaella Melfi

Marco Tutone

Andrea Pace

Ivana Pibiri

Affiliations

Soon will be listed here.

Abstract

This review focuses on the use of oxadiazoles as translational readthrough-inducing drugs (TRIDs) to rescue the functional full-length protein expression in mendelian genetic diseases caused by nonsense mutations. These mutations in specific genes generate premature termination codons (PTCs) responsible for the translation of truncated proteins. After a brief introduction on nonsense mutations and their pathological effects, the features of various classes of TRIDs will be described discussing differences or similarities in their mechanisms of action. Strategies to correct the PTCs will be presented, particularly focusing on a new class of Ataluren-like oxadiazole derivatives in comparison to aminoglycosides. Additionally, recent results on the efficiency of new candidate TRIDs in restoring the production of the cystic fibrosis transmembrane regulator (CFTR) protein will be presented. Finally, a prospectus on complementary strategies to enhance the effect of TRIDs will be illustrated together with a conclusive paragraph about perspectives, opportunities, and caveats in developing small molecules as TRIDs.

Citing Articles

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Readthrough Approach Using NV Translational Readthrough-Inducing Drugs (TRIDs): A Study of the Possible Off-Target Effects on Natural Termination Codons (NTCs) on TP53 and Housekeeping Gene Expression.

Perriera R, Vitale E, Pibiri I, Carollo P, Ricci D, Corrao F Int J Mol Sci. 2023; 24(20).

PMID: 37894764 PMC: 10606485. DOI: 10.3390/ijms242015084.

Site-Specific RNA Editing of Stop Mutations in the CFTR mRNA of Human Bronchial Cultured Cells.

Chiavetta R, Titoli S, Barra V, Cancemi P, Melfi R, Di Leonardo A Int J Mol Sci. 2023; 24(13).

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