Selective targeting of human TET1 by cyclic peptide inhibitors: Insights from biochemical profiling.

Selective targeting of human TET1 by cyclic peptide inhibitors: Insights from biochemical profiling.

Bioorganic & medicinal chemistry (2024-01-24)

Klemensas Šimelis, Hilal Saraç, Eidarus Salah, Kosuke Nishio, Tom E McAllister, Thomas P Corner, Anthony Tumber, Roman Belle, Christopher J Schofield, Hiroaki Suga, Akane Kawamura

PMID38262305

摘要

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.

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产品描述

F1804

Sigma-Aldrich

单克隆抗-FLAG^® M2 小鼠抗, 1.0-1.2 mg/mL, clone M2, affinity isolated antibody, buffered aqueous solution (50% glycerol, 10 mM sodium phosphate, and 150 mM NaCl, pH 7.4)