Domain-Selective BET Ligands Yield Next-Generation Synthetic Genome Readers/Regulators with Nonidentical Cellular Functions

Domain-Selective BET Ligands Yield Next-Generation Synthetic Genome Readers/Regulators with Nonidentical Cellular Functions; Ashraf Mohammed, M. Brett Waddell, Ieva Sutkeviciute, Adithi Danda, Steven J. Philips, Walter Lang, P. Jake Slavish, Sandra J. Kietlinska, Mangesh Kaulage, Das Sourav, and Aseem Z. Ansari; J. Am. Chem. Soc. 2023, XXXX, XXX, XXX-XXX; Publication Date:November 3, 2023; doi:10.1021/jacs.3c06297 

SynTEF1, a prototype synthetic genome reader/regulator (SynGR), was designed to target GAA triplet repeats and restore the expression of frataxin (FXN) in Friedreich’s ataxia patients. 

SynGRs as chemical probes provide unique insights into the molecular recognition principles utilized by natural factors to precisely regulate gene expression, and they guide the design of more sophisticated synthetic gene regulators with greater therapeutic potential.