Chromodomain Ligand Optimization via Target-Class Directed Combinatorial Repurposing.

ABSTRACT: Efforts to develop strategies for small-molecule chemical probe discovery against the readers of the methyl-lysine (Kme) post-translational modification have been met with limited success. Targeted disruption of these protein-protein interactions via peptidomimetic inhibitor optimization is a promising alternative to small-molecule hit discovery; however, recognition of identical peptide motifs by multiple Kme reader proteins presents a unique challenge in the development of selective Kme reader chemical probes. These selectivity challenges are exemplified by the Polycomb repressive complex 1 (PRC1) chemical probe, UNC3866, which demonstrates submicromolar off-target affinity toward the non-PRC1 chromodomains CDYL2 and CDYL. Moreover, since peptidomimetics are challenging subjects for stru

SUBMITTER: Barnash KD 

PROVIDER: S-EPMC5026585 | biostudies-literature | 2016 Sep

REPOSITORIES: biostudies-literature