Discovery of (phenylureido)piperidinyl benzamides as prospective inhibitors of bacterial autolysin E from Staphylococcus aureus

Journal of Enzyme Inhibition and Medicinal Chemistry

Vesna Hodnik¹  Dušan Turk²  Sara Pintar³  Simona Golič Grdadolnik⁴  Marjana Novič⁴  Mitja Ogrizek⁴  Jure Borišek⁴  Andrej Perdih⁴ 

[1] Biotechnical Faculty, Infrastructural Center for Surface Plasmon Resonance, Ljubljana, Slovenia;Department of Biochemistry, Molecular and Structural Biology, Jozef Stefan Institute, Ljubljana, Slovenia;Centre of Excellence for Integrated Approaches in Chemistry and Biology of Proteins, Ljubljana, Sloveni;Department of Biochemistry, Molecular and Structural Biology, Jozef Stefan Institute, Ljubljana, Slovenia;Jozef Stefan International Postgraduate School, Ljubljana, Slovenia;National Institute of Chemistry, Ljubljana, Slovenia;

关键词: Autolysin E;    glycoside hydrolase;    virtual screening;    SPR;    STD NMR;   

DOI  :  10.1080/14756366.2018.1493474

来源: publisher

【 摘 要 】

Autolysin E (AtlE) is a cell wall degrading enzyme that catalyzes the hydrolysis of the β-1,4-glycosidic bond between the N-acetylglucosamine and N-acetylmuramic acid units of the bacterial peptidoglycan. Using our recently determined crystal structure of AtlE from Staphylococcus aureus and a combination of pharmacophore modeling, similarity search, and molecular docking, a series of (Phenylureido)piperidinyl benzamides were identified as potential binders and surface plasmon resonance (SPR) and saturation-transfer difference (STD) NMR experiments revealed that discovered compounds bind to AtlE in a lower micromolar range. (phenylureido)piperidinyl benzamides are the first reported non-substrate-like compounds that interact with this enzyme and enable further study of the interaction of small molecules with bacterial AtlE as potential inhibitors of this target.

【 授权许可】

CC BY