| Autor: |
Comess KM; Department of Target and Lead Discovery, Global Pharmaceutical R&D, Abbott Laboratories, Abbott Park, Illinois 60064-6217, USA. kenneth.m.comess@abbott.com, Schurdak ME, Voorbach MJ, Coen M, Trumbull JD, Yang H, Gao L, Tang H, Cheng X, Lerner CG, McCall JO, Burns DJ, Beutel BA |
| Jazyk: |
angličtina |
| Zdroj: |
Journal of biomolecular screening [J Biomol Screen] 2006 Oct; Vol. 11 (7), pp. 743-54. Date of Electronic Publication: 2006 Sep 14. |
| DOI: |
10.1177/1087057106289971 |
| Abstrakt: |
The authors describe the discovery of a new class of inhibitors to an essential Streptococcus pneumoniae cell wall biosyn-thesis enzyme, MurF, by a novel affinity screening method. The strategy involved screening very large mixtures of diverse small organic molecules against the protein target on the basis of equilibrium binding, followed by iterative ultrafiltration steps and ligand identification by mass spectrometry. Hits from any affinity-based screening method often can be relatively nonselective ligands, sometimes referred to as "nuisance" or "promiscuous" compounds. Ligands selective in their binding affinity for the MurF target were readily identified through electronic subtraction of an empirically determined subset of promiscuous compounds in the library without subsequent selectivity panels. The complete strategy for discovery and identification of novel specific ligands can be applied to all soluble protein targets and a wide variety of ligand libraries. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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