Identification and characterization of ternary complexes consisting of FKBP12, MAPRE1 and macrocyclic molecular glues.

ABSTRACT: Many disease-relevant and functionally well-validated targets are difficult to drug. Their poorly defined 3D structure without deep hydrophobic pockets makes the development of ligands with low molecular weight and high affinity almost impossible. For these targets, incorporation into a ternary complex may be a viable alternative to modulate and in most cases inhibit their function. Therefore, we are interested in methods to identify and characterize molecular glues. In a protein array screen of 50 different macrocyclic FKBP12 ligands against 2500 different randomly selected proteins, a molecular glue compound was found to recruit a dimeric protein called MAPRE1 to FKBP12 in a compound-dependent manner. The corresponding ternary complex was characterized by TR-FRET proximity assay and nati

SUBMITTER: Salcius M 

PROVIDER: S-EPMC11883961 | biostudies-literature | 2025 May

REPOSITORIES: biostudies-literature