SEAL by NMR: Glyco‐Based Selenium‐Labeled Affinity Ligands Detected by NMR Spectroscopy |
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Authors: | Christoffer Hamark Dr Jens Landström Prof?Dr Göran Widmalm |
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Institution: | Arrhenius Laboratory, Department of Organic Chemistry, Stockholm University, 10691 Stockholm (Sweden) |
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Abstract: | We report a method for the screening of interactions between proteins and selenium‐labeled carbohydrate ligands. SEAL by NMR is demonstrated with selenoglycosides binding to lectins where the selenium nucleus serves as an NMR‐active handle and reports on binding through 77Se NMR spectroscopy. In terms of overall sensitivity, this nucleus is comparable to 13C NMR, while the NMR spectral width is ten times larger, yielding little overlap in 77Se NMR spectroscopy, even for similar compounds. The studied ligands are singly selenated bioisosteres of methyl glycosides for which straightforward preparation methods are at hand and libraries can readily be generated. The strength of the approach lies in its simplicity, sensitivity to binding events, the tolerance to additives and the possibility of having several ligands in the assay. This study extends the increasing potential of selenium in structure biology and medicinal chemistry. We anticipate that SEAL by NMR will be a beneficial tool for the development of selenium‐based bioactive compounds, such as glycomimetic drug candidates. |
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Keywords: | 77Se NMR spectroscopy lectins protein– ligand interactions SEAL selenoglycosides |
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