ub.xmlui.mirage2.page-structure.muninLogoub.xmlui.mirage2.page-structure.openResearchArchiveLogo
    • EnglishEnglish
    • norsknorsk
  • Velg spraaknorsk 
    • EnglishEnglish
    • norsknorsk
  • Administrasjon/UB
Vis innførsel 
  •   Hjem
  • Fakultet for naturvitenskap og teknologi
  • Institutt for kjemi
  • Artikler, rapporter og annet (kjemi)
  • Vis innførsel
  •   Hjem
  • Fakultet for naturvitenskap og teknologi
  • Institutt for kjemi
  • Artikler, rapporter og annet (kjemi)
  • Vis innførsel
JavaScript is disabled for your browser. Some features of this site may not work without it.

Discovery of Novel Inhibitor Scaffolds against the Metallo-beta-lactamase VIM-2 by Surface Plasmon Resonance (SPR) Based Fragment Screening

Permanent lenke
https://hdl.handle.net/10037/8958
DOI
https://doi.org/10.1021/acs.jmedchem.5b01289
Thumbnail
Åpne
article.pdf (1.505Mb)
accepted manuscript version (PDF)
Dato
2015-10-17
Type
Journal article
Tidsskriftartikkel
Peer reviewed

Forfatter
Christopeit, Tony; Carlsen, Trine Josefine Olsen; Helland, Ronny; Leiros, Hanna-Kirsti S.
Sammendrag
Metallo-β-lactamase (MBL) inhibitors can restore the function of carbapenem antibiotics and therefore help to treat infections of antibiotic resistant bacteria. In this study, we report novel fragments inhibiting the clinically relevant MBL Verona integron-encoded metallo-β-lactamase (VIM-2). The fragments were identified from a library of 490 fragments using an orthogonal screening approach based on a surface plasmon resonance (SPR) based assay combined with an enzyme inhibition assay. The identified fragments showed IC50 values between 14 and 1500 μM and ligand efficiencies (LE) between 0.48 and 0.23 kcal/mol per heavy atom. For two of the identified fragments, crystal structures in complex with VIM-2 were obtained. The identified fragments represent novel inhibitor scaffolds and are good starting points for the design of potent MBL inhibitors. Furthermore, the established SPR based assay and the screening approach can be adapted to other MBLs and in this way improve the drug discovery process for this important class of drug targets.
Beskrivelse
Accepted manuscript version. Published version at http://doi.org/10.1021/acs.jmedchem.5b01289.
Forlag
American Chemical Society
Sitering
Journal of Medicinal Chemistry 2015, 58(21):8671-8682
Metadata
Vis full innførsel
Samlinger
  • Artikler, rapporter og annet (kjemi) [565]

Bla

Bla i hele MuninEnheter og samlingerForfatterlisteTittelDatoBla i denne samlingenForfatterlisteTittelDato
Logg inn

Statistikk

Antall visninger
UiT

Munin bygger på DSpace

UiT Norges Arktiske Universitet
Universitetsbiblioteket
uit.no/ub - munin@ub.uit.no

Tilgjengelighetserklæring