Gemma Davison, Mathew P Martin, Shannon Turberville, Selma Dormen, Richard Heath, Amy B Heptinstall, Marie Lawson, Duncan C Miller, Yi Min Ng, James N Sanderson, Ian Hope, Daniel J Wood, Céline Cano, Jane A Endicott, Ian R Hardcastle, Martin E M Noble, Michael J Waring
The development of ligands for biological targets is critically dependent on the identification of sites on proteins that bind molecules with high affinity. A set of compounds, called FragLites, can identify such sites, along with the interactions required to gain affinity, by X-ray crystallography. We demonstrate the utility of FragLites in mapping the binding sites of bromodomain proteins BRD4 and ATAD2 and demonstrate that FragLite mapping is comparable to a full fragment screen in identifying ligand binding sites and key interactions...
November 11, 2022: Journal of Medicinal Chemistry