Trimethylsilyl tag for probing protein–ligand interactions by NMR

Walter Becker, Luke A. Adams, Bim Graham, Gabriel E. Wagner, Klaus Zangger, Gottfried Otting, Christoph Nitsche

Research output: Contribution to journalArticleResearchpeer-review

2 Citations (Scopus)

Abstract

Protein–ligand titrations can readily be monitored with a trimethylsilyl (TMS) tag. Owing to the intensity, narrow line shape and unique chemical shift of a TMS group, dissociation constants can be determined from straightforward 1D 1H-NMR spectra not only in the fast but also in the slow exchange limit. The tag is easily attached to cysteine residues and a sensitive reporter of ligand binding also at sites where it does not interfere with ligand binding or catalytic efficiency of the target protein. Its utility is demonstrated for the Zika virus NS2B–NS3 protease and the human prolyl isomerase FK506 binding protein.

Original languageEnglish
Pages (from-to)211-218
Number of pages8
JournalJournal of Biomolecular NMR
Volume70
Issue number4
DOIs
Publication statusPublished - 1 Apr 2018

Keywords

  • Dissociation constant
  • Lead discovery
  • Protein–ligand interactions
  • Slow exchange
  • Trimethylsilyl group

Cite this

Becker, W., Adams, L. A., Graham, B., Wagner, G. E., Zangger, K., Otting, G., & Nitsche, C. (2018). Trimethylsilyl tag for probing protein–ligand interactions by NMR. Journal of Biomolecular NMR, 70(4), 211-218. https://doi.org/10.1007/s10858-018-0173-6