title: A new class of salicylic acid derivatives for inhibiting YopH  of Yersinia pestis.
abstract: Previously, we identified a class of salicylic acid derivatives that display inhibitory activity against the protein tyrosine phosphatase YopH from Yersinia pestis. Because docking study suggested that the large phenyl ring attaching to the salicylic acid core might be exposed to the solvent and might not contribute significantly to binding, we have developed a new class of compounds that no longer contain this phenyl ring. We first devised a synthetic scheme for the compounds and then developed an automated computational screening model surrounding this synthetic scheme to help select a small number of compounds for synthesis and experimental testing. Based on this computational screening model and the analysis of the structure-activity relationship of our previous class of compounds, we have synthesized eight compounds and found five that yield micromolar activity. When applying in a larger scale, the synthetic scheme and the computational screening model developed here should help to identify even more potent inhibitors in the future.
authors.forename: Mahesh P
authors.initials: MP
authors.lastname: Paudyal
authors.forename: Li
authors.initials: L
authors.lastname: Wu
authors.forename: Zhong-Yin
authors.initials: ZY
authors.lastname: Zhang
authors.forename: Christopher D
authors.initials: CD
authors.lastname: Spilling
authors.forename: Chung F
authors.initials: CF
authors.lastname: Wong
mesh_terms: D001425:Bacterial Outer Membrane Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D001665:Binding Sites; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism; D062105:Molecular Docking Simulation; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D017027:Protein Tyrosine Phosphatases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D012459:Salicylates / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism; D013329:Structure-Activity Relationship; D015010:Yersinia pestis / Q000378:metabolism*
chemical_list: D001425:Bacterial Outer Membrane Proteins; D004791:Enzyme Inhibitors; D012459:Salicylates; D017027:Protein Tyrosine Phosphatases; C067571:yopH protein, Yersinia