Discovery of selective 2,4-diaminopyrimidine-based photoaffinity probes for glyoxalase IElectronic supplementary information (ESI) available: Detailed synthetic procedures, 1H and 13C NMR spectra, HPLC chromatograms for compounds L1, L2, L3, L1-Biotin and L1-Bpyne; detailed procedures for biological assays; mass spectroscopy data for GLO-1. See DOI: 10.1039/c3md00286a

Glyoxalase I (GLO-1) plays a critical role in the detoxification of 2-oxoaldehydes and is highly expressed in cancer cells. Through photo-affinity labelling and affinity pull-down approaches, a series of 2,4-diaminopyrimidine compounds were discovered to selectively bind to GLO-1 in cells. These compounds show potent inhibition of GLO-1 enzyme activity and prevent proliferation of cancer cells. The cell permeable and "clickable" photoaffinity probe L1-Bpyne presented here could be a valuable tool for profiling GLO-1 in live cells. L1-Bpyne was discovered as a potent inhibitor and cell permeable probe of glyoxalase I.