Microarray-guided discovery of two-photon (2P) small molecule probes for live-cell imaging of cysteinyl cathepsin activities

A microarray immobilized with 105 aldehyde-containing small molecules was screened against mammalian cell lysates over-expressing cathepsin L to identify two potent inhibitors, which were subsequently converted into cell-permeable probes capable of live-cell imaging of endogenous cysteinyl cathepsin activities by two-photon fluorescence microscopy.