Repurposing Suzuki Coupling Reagents as a Directed Fragment Library Targeting Serine Hydrolases and Related Enzymes

Serine
hydrolases are susceptible to potent reversible inhibition
by boronic acids. Large collections of chemically diverse boronic
acid fragments are commercially available because of their utility
in coupling chemistry. We repurposed the approximately 650 boronic
acid reagents in our collection as a directed fragment library targeting
serine hydrolases and related enzymes. Highly efficient hits (LE >
0.6) often result. The utility of the approach is illustrated with
the results against autotaxin, a phospholipase implicated in cardiovascular
disease.