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Application of Intramolecular O-to-N Phosphoryl Transfer Reaction to Design Fluorogenic Probes to Detect Activities
Risako Sawayama1, Mayano Minoda1, Hirotatsu Kojima2
1Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
Abstract:
We propose the design strategy of fluorogenic probes of proteases/peptidases and acylamino acid hydrolases utilizing an intramolecular O-to-N phosphoryl transfer reaction, in which the main chain of peptides or amino acids is retained from the natural substrate but the side chain was designed to attach the fluorophore. The strategy is useful to design fluorogenic probes for peptidases/proteases that do not prefer the main chain modification and acylamino acid hydrolases. We have developed the fluorogenic substrates for GGT5, GGCT, and PM20D1 and have performed the screening of PM20D1 inhibitors/activators to characterize the compounds that modify the activity of PM20D1.
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