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Exploration of inhibitors of the bacterial LexA repressor-protease.
Jaramillo, Ana Victoria Cheng; Cory, Michael B; Li, Allen; Kohli, Rahul M; Wuest, William M.
Afiliação
  • Jaramillo AVC; Department of Chemistry, Emory University, Atlanta, GA, USA.
  • Cory MB; Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
  • Li A; Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
  • Kohli RM; Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA. Electronic address: rkohli@pennmedicine.upenn.edu.
  • Wuest WM; Department of Chemistry, Emory University, Atlanta, GA, USA. Electronic address: wwuest@emory.edu.
Bioorg Med Chem Lett ; 65: 128702, 2022 06 01.
Article em En | MEDLINE | ID: mdl-35351585
Resistant and tolerant bacterial infections lead to billions in healthcare costs and cause hundreds of thousands of deaths each year. The bulk of current antibiotic research efforts focus on molecules which, although novel, are not immune from acquired resistance and seldomly affect tolerant populations. The bacterial SOS response has been implicated in several resistance and tolerance mechanisms, making it an attractive antibiotic target. Using small molecule inhibitors targeting a key step in the deployment of the SOS response, our approach focused on preventing the deployment of mechanisms such as biofilm formation, horizontal gene transfer, and error-prone DNA repair. Herein we report the synthesis and testing of analogs of a triazole-containing tricyclic inhibitor of LexA proteolysis, the key event in the SOS response. Our results hint that our inhibitor's may function by adopting a ß-hairpin conformation, reminiscent of the native cleavage loop of LexA.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Peptídeo Hidrolases / Resposta SOS em Genética Idioma: En Ano de publicação: 2022 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Peptídeo Hidrolases / Resposta SOS em Genética Idioma: En Ano de publicação: 2022 Tipo de documento: Article