Using tert-Butyl Groups in a Ligand To Identify Its Binding Site on a Protein

作者：Chen, Wan-Na; Otting, Gottfried^*

来源：ACS Medicinal Chemistry Letters, 2018, 9(2): 109-113.

DOI：10.1021/acsmedchemlett.7b00464

• Boc group
• nuclear Overhauser effects
• ligand binding site

Few methods allow determining the binding site of tightly binding ligands. We show that ligands containing a tent-butyl (e.g., Boc) group produce easily observable nuclear Overhauser effects (NOE) with the target protein even when the tert-butyl group is not highly solvent exposed. NOEs with methyl groups of the target protein are readily assigned by selectively isotope labeling, presenting a practical and quick way to pinpoint the location of the ligand without any prior specific nuclear magnetic resonance assignments of the protein. The approach works for nonexchanging ligands as well as for weakly binding ligands.

• 出版日期2018-2
• 单位暨南大学