1. Academic Validation
  2. Using tert-Butyl Groups in a Ligand To Identify Its Binding Site on a Protein

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

  • ACS Med Chem Lett. 2018 Jan 12;9(2):109-113. doi: 10.1021/acsmedchemlett.7b00464.
Wan-Na Chen 1 2 Gottfried Otting 1
Affiliations

Affiliations

  • 1 Research School of Chemistry, Australian National University, Canberra, ACT 2601, Australia.
  • 2 College of Pharmacy, Jinan University, Guangzhou, Guangdong 510632, China.
Abstract

Few methods allow determining the binding site of tightly binding ligands. We show that ligands containing a tert-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.

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