Journal of Biomolecular NMR

, Volume 21, Issue 4, pp 349–359

WaterLOGSY as a method for primary NMR screening: Practical aspects and range of applicability

  • Claudio Dalvit
  • GianPaolo Fogliatto
  • Albert Stewart
  • Marina Veronesi
  • Brian Stockman
Article

Abstract

WaterLOGSY represents a powerful method for primary NMR screening in the identification of compounds interacting with macromolecules, including proteins and DNA or RNA fragments. Several relay pathways are used constructively in the experiment for transferring bulk water magnetization to the ligand. The method is particularly useful for the identification of novel scaffolds of micromolar affinity that can be then optimized using directed screening, combinatorial chemistry, medicinal chemistry and structure-based drug design. The practical aspects and range of applicability of the WaterLOGSY experiment are analyzed in detail here. Competition binding and titration WaterLOGSY permit, after proper correction, the evaluation of the dissociation binding constant. The high sensitivity of the technique in combination with the easy deconvolution of the mixtures for the identification of the active components, significantly reduces the amount of material and time needed for the NMR screening process.

dissociation binding constant drug design magnetization transfer NMR screening protein-ligand interactions Water-Ligand Observed via Gradient SpectroscopY WaterLOGSY 

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Copyright information

© Kluwer Academic Publishers 2001

Authors and Affiliations

  • Claudio Dalvit
    • 1
  • GianPaolo Fogliatto
    • 2
  • Albert Stewart
    • 2
  • Marina Veronesi
    • 1
  • Brian Stockman
    • 3
  1. 1.ChemistryItaly
  2. 2.Biology Department, PharmaciaNervianoItaly
  3. 3.Structural, Analytical & Medicinal Chemistry DepartmentPharmaciaKalamazooU.S.A

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