Sökning: WFRF:(Danielson U Helena) >
Identification of M...
Identification of MMP-12 Inhibitors by Using Biosensor-Based Screening of a Fragment Library
-
- Nordström, Helena (författare)
- Uppsala universitet,Institutionen för biokemi och organisk kemi
-
- Gossas, Thomas (författare)
- Uppsala universitet,Institutionen för biokemi och organisk kemi
-
Hämäläinen, Markku (författare)
-
visa fler...
-
Källblad, Per (författare)
-
Nyström, Susanne (författare)
-
Wallberg, Hans (författare)
-
- Danielson, U. Helena, 1959- (författare)
- Uppsala universitet,Institutionen för biokemi och organisk kemi
-
visa färre...
-
(creator_code:org_t)
- 2008-05-22
- 2008
- Engelska.
-
Ingår i: Journal of Medicinal Chemistry. - : American Chemical Society (ACS). - 0022-2623 .- 1520-4804. ; 51:12, s. 3449-3459
- Relaterad länk:
-
https://urn.kb.se/re...
-
visa fler...
-
https://doi.org/10.1...
-
visa färre...
Abstract
Ämnesord
Stäng
- Small inhibitors of matrix metalloproteinase 12 (MMP-12) have been identified with a biosensor-based screening strategy and a specifically designed fragment library. The interaction between fragments and three variants of the target and a reference protein with an active-site zinc ion was measured continuously by surface plasmon resonance. The developed experimental design overcame the inherent instability of MMP-12 and allowed the identification of fragments that interacted specifically with the active-site of MMP-12 but not with the reference protein. The interaction with MMP-12 for selected compounds were analyzed for concentration dependence and saturability. Compounds interacting distinctly with the target were further evaluated by an activity-based assay, verifying MMP-12 inhibition. Two effective inhibitors were identified, and the compound with highest affinity was confirmed to be a competitive inhibitor with an IC50 of 290 nM and a ligand efficiency of 0.7 kcal/mol heavy atom. This procedure integrates selectivity and binding site identification into the screening procedure and does not require structure determination.
Nyckelord
- Biochemistry
- Biokemi
- Biokemi
- Biochemistry
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
Hitta via bibliotek
Till lärosätets databas