Protein-Templated Hit Identification through an Ugi Four-Component Reaction

Abstract

The Ugi four-component reaction (Ugi-4CR) was employed as a new reaction in kinetic target-guided synthesis (KTGS). Applying the reaction on the bacterial β sliding clamp (DnaN) (middle) resulted in marked acceleration of product assembly from a library of eight building blocks representing four chemical classes. UPLC-HRMS analysis of the in situ Ugi-4CR in the presence of the strong inhibitor griselimycin (left) or using endothiapepsin (right) as an unrelated protein revealed no product formation, demonstrating the specificity of the DnaN-templated reaction. For more details see the Full paper by A. K. H. Hirsch et al. on page 14585 ff.