DAVIS, Calif.—To identify new anti-infectives, researchers at University of California-Davis and Central Connecticut State University recently took a cue from the statin drugs, using one-bead one-compound combinatorial libraries to link substrate analogues to chemical moieties that enhance active-site binding. The researchers targeted a key enzyme in the shikimate pathway, which is absent in humans but critical to microbial survival.

 

As they reported in the Journal of Medicinal Chemistry, the researchers generated a bead library of amino acids and acids to a stable analogue of chorismate, the product of ADCS. They then presorted the library to eliminate autofluorescent molecules, and combined the remaining library members with fluorescently labeled ADCS, using COPAS sorting to automatically select enzyme-bound beads.