SALMON: Solvent Accessibility, Ligand binding, and Mapping of ligand Orientation by NMR Spectroscopy

• Published in: Journal of medicinal chemistry Vol. 51; no. 1; pp. 1 - 3
• Main Authors: Ludwig, Christian, Michiels, Paul J. A, Wu, Xiaoqiu, Kavanagh, Kathryn L, Pilka, Ewa, Jansson, Anna, Oppermann, Udo, Günther, Ulrich L
• Format: Journal Article
• Language: English
• Published: Washington, DC American Chemical Society 10.01.2008
• Subjects: Antineoplastic Agents - chemistry; Aziridines - chemistry; Binding Sites; Biological and medical sciences; Ligands; Magnetic Resonance Spectroscopy; Medical sciences; Miscellaneous; Models, Molecular; NAD(P)H Dehydrogenase (Quinone) - chemistry; Pharmacology. Drug treatments; Prodrugs - chemistry; Protein Binding; Solvents; Water - chemistry; Antineoplastic agent; Ligand binding; Enzyme; Solvent accessibility; Ligand; Molecular model; Molecular interaction; NMR spectrometry; Oxidoreductases; Tretazicar; Modeling; Conformation
• ISSN: 0022-2623; 1520-4804
• DOI: 10.1021/jm701020f

Quinone oxidoreductase 2 (NQO2) binds the prodrug tretazicar (also known as CB1954, 5-(aziridin-1-yl)-2,4-dinitrobenzamide), which exhibits a profound antitumor effect in human cancers when administered together with caricotamide. X-ray structure determination allowed for two possible orientations of the ligand. Here we describe a new NMR method, SALMON (solvent accessibility, ligand binding, and mapping of ligand orientation by NMR spectroscopy), based on waterLOGSY to determine the orientation of a ligand bound to a protein by mapping its solvent accessibility, which was used to unambiguously determine the orientation of CB1954 in NQO2.