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Cyclobutanone Inhibitors of Diaminopimelate Desuccinylase (DapE) as Potential New Antibiotics.
Habeeb Mohammad, Thahani S; Kelley, Emma H; Reidl, Cory T; Konczak, Katherine; Beulke, Megan; Javier, Janielle; Olsen, Kenneth W; Becker, Daniel P.
Afiliación
  • Habeeb Mohammad TS; Department of Chemistry and Biochemistry, Loyola University Chicago, 1032 West Sheridan Road, Chicago, IL 60660, USA.
  • Kelley EH; Department of Chemistry and Biochemistry, Loyola University Chicago, 1032 West Sheridan Road, Chicago, IL 60660, USA.
  • Reidl CT; Department of Chemistry and Biochemistry, Loyola University Chicago, 1032 West Sheridan Road, Chicago, IL 60660, USA.
  • Konczak K; Department of Chemistry and Biochemistry, Loyola University Chicago, 1032 West Sheridan Road, Chicago, IL 60660, USA.
  • Beulke M; Department of Chemistry and Biochemistry, Loyola University Chicago, 1032 West Sheridan Road, Chicago, IL 60660, USA.
  • Javier J; Department of Chemistry and Biochemistry, Loyola University Chicago, 1032 West Sheridan Road, Chicago, IL 60660, USA.
  • Olsen KW; Department of Chemistry and Biochemistry, Loyola University Chicago, 1032 West Sheridan Road, Chicago, IL 60660, USA.
  • Becker DP; Department of Chemistry and Biochemistry, Loyola University Chicago, 1032 West Sheridan Road, Chicago, IL 60660, USA.
Int J Mol Sci ; 25(2)2024 Jan 22.
Article en En | MEDLINE | ID: mdl-38279338
ABSTRACT
Based on our previous success in using cyclobutanone derivatives as enzyme inhibitors, we have designed and prepared a 37-member library of α-aminocyclobutanone amides and sulfonamides, screened for inhibition of the bacterial enzyme diaminopimelate desuccinylase (DapE), which is a promising antibiotic target, and identified several inhibitors with micromolar inhibitory potency. Molecular docking suggests binding of the deprotonated hydrate of the strained cyclobutanone, and thermal shift analysis with the most potent inhibitor (3y, IC50 = 23.1 µM) enabled determination of a Ki value of 10.2 +/- 0.26 µM and observed two separate Tm values for H. influenzae DapE (HiDapE).
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Inhibidores Enzimáticos / Antibacterianos Idioma: En Revista: Int J Mol Sci Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Suiza
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Inhibidores Enzimáticos / Antibacterianos Idioma: En Revista: Int J Mol Sci Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Suiza