Fig. 1: Sulphostin binds to DPP proteins.
From: Sulphostin-inspired N-phosphonopiperidones as selective covalent DPP8 and DPP9 inhibitors
a The crystal structures of DPP8 and 9 in the apo state in an overlay, with DPP9 shown in blue and DPP8 in brown as a ribbon model. The active site was zoomed in, showing the active site residues of DPP4 (green), DPP8 (brown) and DPP9 (blue) as stick model. Backbone of DPP9 is shown in blue as ribbon model. Crystal structures from PDB: 1PFQ (DPP4), 6EOO (DPP8) and 6EOQ (DPP9). b Chemical structure of the natural product Sulphostin (1) containing a phosphosulfamate functional group (indicated in black) and the (S)−3-aminopiperidine-2-one group in purple. c Native MS spectrum of DPP9 in the dimeric state with or without Sulphostin bound. Peaks correspond to different charge states. The charge state distribution for the dimer without inhibitor bound is shown in blue, whereas the distribution for the DPP9 dimer with one Sulphostin molecule is shown in light brown and for two Sulphostin molecules in dark brown. d Kinetic analysis of DPP inhibition by Sulphostin. The pseudo-first order rate constant (kobs) was calculated from an exponential regression of progress curves and plotted against the inhibitor concentration. KI and kinact were obtained via fitting to a hyperbolic equation. All activity measurements were performed in triplicate (n = 3 technical replicates), mean values are shown and error bars indicate the standard error of the mean (SEM). Source data are provided as a Source Data file.
