Saturation transfer difference spectroscopy

From NMR Wiki

Saturation transfer difference (STD) spectroscopy allows to detect transient binding of small molecule ligands to macromolecular receptors. Receptor species include proteins - free in solution or immobilized, whole virus particles, etc.

Range of applicable dissociation constants is approximately 10^-3-10^-8 M [1].

STD method can be used to determine which part of the ligand molecule is responsible for binding, since most strongly interacting groups of ligand will show stronger STD effect.

Method of saturation transfer difference relies on the possibility to selectively saturate protons of macromolecular receptor by irradiating the spectral region containing "wings" of broad resonances of the macromolecule which is also free of any smaller molecule signals. Due to effective spin diffusion saturation quickly propagates across the entire receptor. If the smaller molecule ligand binds the receptor, saturation will also spread onto the ligand. The result will be that intensity of the ligand signal will be attenuated. Substraction of resulting spectrum from the reference spectrum without saturation yields the STD spectrum containing only signals of the binding ligands.

References

1. Mayer, M and Meyer, B. Group epitope mapping by saturation transfer difference NMR to identify segments of a ligand in direct contact with a protein receptor. J Am Chem Soc 123(25):6108--17, 2001. BibTeX [mayer01]

2. Meyer, B and Peters, T. NMR Spectroscopy Techniques for Screening and Identifying Ligand Binding to Protein Receptors. Angewandte Chemie International Edition 42(8):864--890, 2003. BibTeX [meyer03]

3. MAYER, M and MEYER, B. CHARACTERIZATION OF LIGAND BINDING BY SATURATION TRANSFER DIFFERENCE NMR SPECTROSCOPY. Angewandte Chemie(International ed Print) 38(12):1784--1788, 1999. BibTeX [meyer99]

4. Streiff, JH and Juranic, NO and Macura, SI and Warner, DO and Jones, KA and Perkins, WJ. Saturation transfer difference nuclear magnetic resonance spectroscopy as a method for screening proteins for anesthetic binding. Mol Pharmacol 66:929--935, 2004. BibTeX [stre04]