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J Am Chem Soc. 2012 Jul 11;134(27):11076-9. doi: 10.1021/ja303301w. Epub 2012 Jun 27.

Boosting the sensitivity of ligand-protein screening by NMR of long-lived states.

Author information

1
Institut des Sciences et Ingénierie Chimiques, Ecole Polytechnique Fédérale de Lausanne, 1015 Lausanne, Switzerland.

Abstract

A new NMR method for the study of ligand-protein interactions exploits the unusual lifetimes of long-lived states (LLSs). The new method provides better contrast between bound and free ligands and requires a protein-ligand ratio ca. 25 times lower than for established T(1ρ) methods, thus saving on costly proteins. The new LLS method was applied to the screening of inhibitors of urokinase-type plasminogen activator (uPA), which is a prototypical target of cancer research. With only 10 μM protein, a dissociation constant (K(D)) of 180 ± 20 nM was determined for the strong ligand (inhibitor) UK-18, which can be compared with K(D) = 157 ± 39 nM determined by the established surface plasmon resonance method.

PMID:
22686687
DOI:
10.1021/ja303301w
[Indexed for MEDLINE]

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