Protein structure-based design of chemical probes for the m6A-mRNA reader YTHDC1

DOI

N6-methyladenosine (m6A), the most prevalent internal modification in eukaryotic messenger RNA, plays a crucial role in numerous biological processes. m6A reader proteins, which recognize and interpret these modifications, serve as key mediators in epitranscriptomic regulation. Using computational modeling, structure-based drug design, and high-throughput screening techniques we have identified lead compounds against the modulators of m6A. With this proposal we aim to further develop our lead compounds into highly potent and selective chemical probes targeting the nuclear m6A-mRNA reader protein YTHDC1. These chemical probes illuminate protein-RNA interactions, revealing epitranscriptomic regulation mechanisms. By manipulating m6A reader proteins, they enable targeted therapies for diseases driven by dysregulated epitranscriptomic processes.

Identifier
DOI https://doi.org/10.15151/ESRF-ES-1473946921
Metadata Access https://icatplus.esrf.fr/oaipmh/request?verb=GetRecord&metadataPrefix=oai_datacite&identifier=oai:icatplus.esrf.fr:inv/1473946921
Provenance
Creator Francesco NAI ORCID logo; Andrew MCCARTHY ORCID logo; Amedeo CAFLISCH ORCID logo
Publisher ESRF (European Synchrotron Radiation Facility)
Publication Year 2027
Rights CC-BY-4.0; https://creativecommons.org/licenses/by/4.0
OpenAccess true
Representation
Resource Type Data from large facility measurement; Collection
Discipline Particles, Nuclei and Fields