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. Author manuscript; available in PMC: 2012 Jun 4.
Published in final edited form as: J Biol Chem. 2007 Jun 1;282(32):23129–23139. doi: 10.1074/jbc.M701857200

FIGURE 1. HTS of sortase and cheminformatics.

FIGURE 1

A, a fluorescence resonance energy transfer-based assay using a-LPETG-d as sortase substrate in a 384-well plate format was used in this HTS (Z′-factor of 0.94). The inset demonstrates the assay design used to identify sortase inhibitors. B, compounds displaying inhibition ≥20% of mean positive control (6,154) were computationally filtered to remove reactive inhibitors, promiscuous inhibitors, etc. (see “Experimental Procedures”). Filtered molecules were placed in a Salvage set, and remaining Lead-like actives were clustered and sampled based on lead-likeness and potential for later SAR analysis, with emphasis on the most active compounds. Approximately 210 “clean” compounds were selected from the Lead-like Clusters. To allow for discovery of chemical tools as well (54), these were combined with representatives from the Salvage set (after their re-clustering) to yield a final set of 407 compounds to take into the secondary screen for specificity.