Structural highlights
Publication Abstract from PubMed
The spread of antibiotic resistant bacteria is a global threat that shakes the foundations of modern healthcare. beta-Lactamases are enzymes that confer resistance to beta-lactam antibiotics in bacteria, and there is a critical need for new inhibitors of these enzymes for combination therapy together with an antibiotic. With this in mind, we have screened a library of 490 fragments to identify starting points for the development of new inhibitors of the class D beta-lactamase oxacillinase-48 (OXA-48) through surface plasmon resonance (SPR), dose-rate inhibition assays, and X-ray crystallography. Furthermore, we have uncovered structure-activity relationships and used alternate conformations from a crystallographic structure to grow a fragment into a more potent compound with a KD of 50 muM and an IC50 of 18 muM.
Screening and Design of Inhibitor Scaffolds for the Antibiotic Resistance Oxacillinase-48 (OXA-48) through Surface Plasmon Resonance Screening.,Lund BA, Christopeit T, Guttormsen Y, Bayer A, Leiros HS J Med Chem. 2016 May 20. PMID:27165692[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Lund BA, Christopeit T, Guttormsen Y, Bayer A, Leiros HS. Screening and Design of Inhibitor Scaffolds for the Antibiotic Resistance Oxacillinase-48 (OXA-48) through Surface Plasmon Resonance Screening. J Med Chem. 2016 May 20. PMID:27165692 doi:http://dx.doi.org/10.1021/acs.jmedchem.6b00660
