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

doi:10.1007/s10858-018-0173-6

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^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

9 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 language	English
Pages (from-to)	211-218
Number of pages	8
Journal	Journal of Biomolecular NMR
Volume	70
Issue number	4
DOIs	https://doi.org/10.1007/s10858-018-0173-6
Publication status	Published - 1 Apr 2018

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title = "Trimethylsilyl tag for probing protein–ligand interactions by NMR",

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.",

keywords = "Dissociation constant, Lead discovery, Protein–ligand interactions, Slow exchange, Trimethylsilyl group",

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T1 - Trimethylsilyl tag for probing protein–ligand interactions by NMR

AU - Becker, Walter

AU - Adams, Luke A.

AU - Graham, Bim

AU - Wagner, Gabriel E.

AU - Zangger, Klaus

AU - Otting, Gottfried

AU - Nitsche, Christoph

PY - 2018/4/1

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AB - 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.

KW - Dissociation constant

KW - Lead discovery

KW - Protein–ligand interactions

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KW - Trimethylsilyl group

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DO - 10.1007/s10858-018-0173-6

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Trimethylsilyl tag for probing protein–ligand interactions by NMR

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