Selective targeting of human TET1 by cyclic peptide inhibitors: Insights from biochemical profiling.
Bioorg Med Chem
; 99: 117597, 2024 Feb 01.
Article
em En
| MEDLINE
| ID: mdl-38262305
ABSTRACT
Ten-Eleven Translocation (TET) enzymes are Fe(II)/2OG-dependent oxygenases that play important roles in epigenetic regulation, but selective inhibition of the TETs is an unmet challenge. We describe the profiling of previously identified TET1-binding macrocyclic peptides. TiP1 is established as a potent TET1 inhibitor (IC50 = 0.26 µM) with excellent selectivity over other TETs and 2OG oxygenases. TiP1 alanine scanning reveals the critical roles of Trp10 and Glu11 residues for inhibition of TET isoenzymes. The results highlight the utility of the RaPID method to identify potent enzyme inhibitors with selectivity over closely related paralogues. The structure-activity relationship data generated herein may find utility in the development of chemical probes for the TETs.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Peptídeos Cíclicos
/
Dioxigenases
Limite:
Humans
Idioma:
En
Revista:
Bioorg Med Chem
Ano de publicação:
2024
Tipo de documento:
Article