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Journal of Biomolecular NMR

, Volume 43, Issue 4, pp 211–217 | Cite as

Time efficient detection of protein–ligand interactions with the polarization optimized PO-WaterLOGSY NMR experiment

  • Alvar D. Gossert
  • Christelle Henry
  • Marcel J. J. Blommers
  • Wolfgang Jahnke
  • César FernándezEmail author
Article

Abstract

The identification of compounds that bind to a protein of interest is of central importance in contemporary drug research. For screening of compound libraries, NMR techniques are widely used, in particular the Water-Ligand Observed via Gradient SpectroscopY (WaterLOGSY) experiment. Here we present an optimized experiment, the polarization optimized WaterLOGSY (PO-WaterLOGSY). Based on a water flip-back strategy in conjunction with model calculations and numerical simulations, the PO-WaterLOGSY is optimized for water polarization recovery. Compared to a standard setup with the conventional WaterLOGSY, time consuming relaxation delays have been considerably shortened and can even be omitted through this approach. Furthermore, the robustness of the pulse sequence in an industrial setup was increased by the use of hard pulse trains for selective water excitation and water suppression. The PO-WaterLOGSY thus yields increased time efficiency by factor of 3–5 when compared with previously published schemes. These time savings have a substantial impact in drug discovery, since significantly larger compound libraries can be tested in screening campaigns.

Keywords

Drug design NMR screening Protein–ligand interactions WaterLOGSY Water handling 

Notes

Acknowledgements

We would like to thank Sebiastian Hiller, Claudio Dalvit and Helena Kovacs for stimulating discussions, and Sandra Jacob and Hans Widmer for critical reading of the manuscript. The authors are indebted to Alain Dietrich for his excellent technical support.

Supplementary material

10858_2009_9303_MOESM1_ESM.pdf (14 kb)
Supplementary material 1 (PDF 14 kb)

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Copyright information

© Springer Science+Business Media B.V. 2009

Authors and Affiliations

  • Alvar D. Gossert
    • 1
  • Christelle Henry
    • 1
  • Marcel J. J. Blommers
    • 1
  • Wolfgang Jahnke
    • 1
  • César Fernández
    • 1
    Email author
  1. 1.Novartis Institutes for Biomedical ResearchBaselSwitzerland

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