Polarization Transfer from Ligands Hyperpolarized by Dissolution Dynamic Nuclear Polarization for Screening in Drug Discovery

Hlaing Min, Giridhar Sekar, Christian Hilty

Research output: Contribution to journalArticlepeer-review

22 Scopus citations

Abstract

Nuclear magnetic resonance (NMR) spectroscopy is a valuable technique for ligand screening, because it exhibits high specificity toward chemical structure and interactions. Dissolution dynamic nuclear polarization (DNP) is a recent advance in NMR methodology that enables the creation of non-equilibrium spin states, which can dramatically increase NMR sensitivity. Here, the transfer of such spin polarization from hyperpolarized ligand to protein is observed. Mixing hyperpolarized benzamidine with the serine protease trypsin, a "fingerprint" of enhanced protein signals is observed, which shows a different intensity profile than the equilibrium NMR spectrum of the protein, but coincides closely to the frequency profile of a saturation transfer difference (STD) NMR experiment. The DNP experiment benefits from hyperpolarization and enables observation of all frequencies in a single, rapid experiment. Based on these merits, it is an interesting alternative to the widely used STD experiment for identification of protein-ligand interactions.

Original languageEnglish (US)
Pages (from-to)1559-1563
Number of pages5
JournalChemMedChem
Volume10
Issue number9
DOIs
StatePublished - Sep 1 2015

Keywords

  • NMR spectroscopy
  • hyperpolarization
  • ligand binding
  • saturation transfer difference

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Pharmacology
  • Drug Discovery
  • Pharmacology, Toxicology and Pharmaceutics(all)
  • Organic Chemistry

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