Virtual screening and experimental validation of a METTL3-targeting peptide with in vitro antiproliferative activity against non-small cell lung cancer cells

Résumé fourni par la source

The METTL3–METTL14 protein–protein interaction (PPI) plays an important role in tumour progression, and disruption of this interaction has been explored as a potential strategy. In this study, four peptides were identified from a peptide database through virtual screening and molecular docking. Among them, peptide-1 showed the lowest Kd value among the tested peptides in MST analysis (Kd = 0.76 ± 0.02 μM). Binding mode analysis, molecular dynamics simulations, and MM/PBSA calculations suggested that peptide-1 might form a binding-related conformation with METTL3 under the simulated conditions. In lung cancer cells, peptide-1 showed growth-inhibitory activity, whereas weaker effects were observed in BEAS-2B cells. Peptide-1 also reduced the METTL3–METTL14-associated NanoBRET signal, decreased cellular m6A levels and JUNB mRNA expression, and its antiproliferative effect was attenuated by METTL3 knockdown. These findings suggest that peptide-1 may represent a METTL3-targeting peptide candidate for further evaluation.

Ce résumé expose les affirmations des auteurs. BNTIC ne l’interprète pas comme une validation indépendante des résultats.