Rapid development of a potent photo-triggered inhibitor of the serine hydrolase RBBP9.
The serine hydrolases constitute a large class of enzymes that play important roles in physiology. There is great interest in the development of potent and selective pharmacological inhibitors of these proteins. Traditional active-site inhibitors often have limited selectivity within this superfamily and are tedious and expensive to discover. Using the serine hydrolase RBBP9 as a model target, we designed a rapid and relatively inexpensive route to highly selective peptoid-based inhibitors that can be activated by visible light. This technology provides rapid access to photo-activated tool compounds capable of selectively blocking the function of particular serine hydrolases.
Department of Chemistry, The Scripps Research Institute, 130 Scripps Way, Jupiter, FL 33458, USA.
Xiaodan
X
Liu
Melissa
M
Dix
Anna E
AE
Speers
Daniel A
DA
Bachovchin
Andrea M
AM
Zuhl
Benjamin F
BF
Cravatt
Thomas J
TJ
Kodadek
D020134:Catalytic Domain; D018797:Cell Cycle Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000378:metabolism; D004801:Eosine Yellowish-(YS) / Q000737:chemistry; D019793:Fluorescein / Q000737:chemistry; D006367:HeLa Cells; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D008027:Light; D008280:Magnetics; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D034444:Peptoids / Q000138:chemical synthesis / Q000737:chemistry; D011485:Protein Binding; D020543:Proteome / Q000378:metabolism; D012428:Ruthenium / Q000737:chemistry
D018797:Cell Cycle Proteins; D004791:Enzyme Inhibitors; D047908:Intracellular Signaling Peptides and Proteins; D009363:Neoplasm Proteins; D034444:Peptoids; D020543:Proteome; C485185:RBBP9 protein, human; D012428:Ruthenium; D004801:Eosine Yellowish-(YS); D019793:Fluorescein