Peptides Targeting RNA m 6 A Methylations Influence the Viability of Cancer Cells.
Rushdhi RauffSudeshi M AbedeeraStefani SchmockerJiale XieSanjaya C AbeysirigunawardenaPublished in: ChemMedChem (2023)
N6-methyladenosine (m 6 A) is the most abundant nucleotide modification observed in eukaryotic mRNA. Changes in m 6 A levels in transcriptome are tightly correlated to expression levels of m 6 A methyltransferases and demethylases. Abnormal expression levels of methyltransferases and demethylases are observed in various diseases and health conditions such as cancer, male infertility, and obesity. This research explores the efficacy of m 6 A-modified RNA as an anticancer drug target. We discovered a 12-mer peptide that binds specifically to m 6 A-modified RNA using phage display experiments. Our fluorescence-based assays illustrate the selected peptide binds to methylated RNA with lower micromolar affinity and inhibit the binding of protein FTO, a demethylase enzyme specific to m 6 A modification. When cancer cell lines were treated with mtp1, it led to an increase in m 6 A levels and a decrease in cell viability. Hence our results illustrate the potential of mtp1 to be developed as a drug for cancer.
Keyphrases
- papillary thyroid
- squamous cell
- poor prognosis
- binding protein
- healthcare
- public health
- gene expression
- metabolic syndrome
- type diabetes
- weight loss
- childhood cancer
- emergency department
- high throughput
- young adults
- small molecule
- mass spectrometry
- cystic fibrosis
- adverse drug
- dna methylation
- social media
- high fat diet induced
- protein protein
- electronic health record