Designing better coumarin-based fluorogenic substrates for PTP1B

As part of a program to develop better PTP1B fluorogenic substrates that more closely mimic the functionality found in the natural substrate, we have prepared and evaluated nine novel analogs of 4-methylumbelliferone phosphate (MUP) with a variety of additional groups occupying the second phosphate binding pocket.

Graphical abstractWe have prepared and evaluated nine novel analogs of 4-methylumbelliferone phosphate (MUP) with a variety of additional groups occupying the second phosphate binding pocket of PTP1B. Surprisingly, the simple benzyl ester 2 was an equivalent substrate for the enzyme as phosphotyrosine mimic 14.Figure optionsDownload full-size imageDownload as PowerPoint slide