High-throughput NMR-based screening with competition binding experiments

Claudio Dalvit, Maria Flocco, Stefan Knapp, Marina Mostardini, Rita Perego, Brian J. Stockman, Marina Veronesi, Mario Varasi

Research output: Contribution to journalArticlepeer-review


The Achille's heel of ligand-based NMR screening methods is their failure to detect high-affinity ligands and molecules that bind covalently to the receptor. We have developed a novel approach for performing high-throughput screening with NMR spectroscopy that overcomes this limitation. The method also permits detection of potential high-affinity molecules that are only marginally soluble, thus significantly enlarging the diversity of compounds amenable to NMR screening. The techniques developed utilize transverse and/or selective longitudinal relaxation parameters in combination with competition binding experiments. Mathematical expressions are derived for proper setup of the NMR experiments and for extracting an approximate value of the binding constant for the identified ligand from a single-point measurement. With this approach it is possible to screen thousands of compounds in a short period of time against protein or DNA and RNA fragments. The methodology can also be applied for screening plant and fungi extracts.

Original languageEnglish
Pages (from-to)7702-7709
Number of pages8
JournalJournal of the American Chemical Society
Issue number26
Publication statusPublished - Jul 3 2002

ASJC Scopus subject areas

  • Chemistry(all)


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