Derivatives of salicylic acid as inhibitors of YopH in Yersinia pestis.

ABSTRACT: Yersinia pestis causes diseases ranging from gastrointestinal syndromes to bubonic plague and could be misused as a biological weapon. As its protein tyrosine phosphatase YopH has already been demonstrated as a potential drug target, we have developed two series of forty salicylic acid derivatives and found sixteen to have micromolar inhibitory activity. We designed these ligands to have two chemical moieties connected by a flexible hydrocarbon linker to target two pockets in the active site of the protein to achieve binding affinity and selectivity. One moiety possessed the salicylic acid core intending to target the phosphotyrosine-binding pocket. The other moiety contained different chemical fragments meant to target a nearby secondary pocket. The two series of compounds differed by hav

SUBMITTER: Huang Z 

PROVIDER: S-EPMC2908532 | biostudies-literature | 2010 Aug

REPOSITORIES: biostudies-literature