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  • Associate Professor
  • Clinical Research Assistant
  • Clinician Researcher
  • Department Manager
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  • Lab assistant
  • Non-permanent Researcher
  • Permanent Researcher
  • Pharmacist
  • PhD Student
  • Physician
  • Post-doc
  • Project Manager
  • Research Associate
  • Research Engineer
  • Retired scientist
  • Technician
  • Undergraduate Student
  • Veterinary
  • Visiting Scientist
  • Deputy Director of Center
  • Deputy Director of Department
  • Deputy Director of National Reference Center
  • Deputy Head of Facility
  • Director of Center
  • Director of Department
  • Director of Institute
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Scientific Fields
Diseases
Organisms
Applications
Technique

Published in ACS chemical biology - 01 Jun 2022

Erdmann D, Contreras J, Le Meur RA, Vitorge B, Saverat V, Tafit A, Jallet C, Cadet-Daniel V, Bon C, Phansavath P, Ratovelomanana-Vidal V, Jeltsch A, Vichier-Guerre S, Guijarro JI, Arimondo PB,

Link to Pubmed [PMID] – 35649238

Link to DOI – 10.1021/acschembio.1c00959

ACS Chem Biol 2022 Jun; ():

Epigenetics has received much attention in the past decade. Many insights on epigenetic (dys)regulation in diseases have been obtained, and clinical therapies targeting them are in place. However, the readers of the epigenetic marks are lacking enlightenment behind this revolution, and it is poorly understood how DNA methylation is being read and translated to chromatin function and cellular responses. Chemical probes targeting the methyl-CpG readers, such as the methyl-CpG binding domain proteins (MBDs), could be used to study this mechanism. We have designed analogues of 5-methylcytosine to probe the MBD domain of human MBD2. By setting up a protein thermal shift assay and an AlphaScreen-based test, we were able to identify three fragments that bind MBD2 alone and disrupt the MBD2-methylated DNA interactions. Two-dimensional NMR experiments and virtual docking gave valuable insights into the interaction of the ligands with the protein showing that the compounds interact with residues that are important for DNA recognition. These constitute the starting point for the design of potent chemical probes for MBD proteins.

https://pubmed.ncbi.nlm.nih.gov/35649238