Design of a fluorescent ligand targeting the S-adenosylmethionine binding site of the histone methyltransferase MLL1.

ABSTRACT: The histone methyltransferase MLL1 has been linked to translocation-associated gene fusion in childhood leukemias and is an attractive drug target. High-throughput biochemical analysis of MLL1 methyltransferase activity requires the production of at least a trimeric complex of MLL1, RbBP5 and WDR5 to elicit robust activity. Production of trimeric and higher order MLL1 complexes in the quantities and reproducibility required for high-throughput screening presents a significant impediment to MLL1 drug discovery efforts. We present here a small molecule fluorescent ligand (FL-NAH, 6) that is able to bind to the S-adenosylmethionine (SAM) binding site of MLL1 in a manner independent of the associated complex members. We have used FL-NAH to develop a fluorescence polarization-based SAM displace

SUBMITTER: Luan Y 

PROVIDER: S-EPMC4689628 | biostudies-literature | 2016 Jan

REPOSITORIES: biostudies-literature