Open AccessScreening Mixtures for Biological Activity by NMR
Author(s) -
Meyer Bernd,
Weimar Thomas,
Peters Thomas
Publication year - 1997
Publication title -
european journal of biochemistry
Language(s) - English
Resource type - Journals
eISSN - 1432-1033
pISSN - 0014-2956
DOI - 10.1111/j.1432-1033.1997.t01-1-00705.x
Subject(s) - chemistry , molecule , biological activity , small molecule , biomolecule , stereochemistry , nuclear overhauser effect , chemical shift , nuclear magnetic resonance spectroscopy , computational chemistry , biochemistry , in vitro , organic chemistry
Development of new drugs often involves the screening of compound libraries for biological activity. Currently, the biologically active component can only be identified if either a pure compound is being tested or if the components of a mixture are spatially separated, for example, on beads. Here, we present an NMR technique based on the transferred nuclear Overhauser effect (transfer NOE) that allows identification and structural characterization of biologically active molecules from a mixture. As an example we demonstrate that from mixtures of oligosaccharides only α‐ l ‐Fuc‐(1→6)‐β‐ d ‐GlcNAc‐OMe binds to Aleuria aurantia agglutinin. The sign of transferred NOEs is opposite to NOEs of small molecules that do not bind to the protein and, thus, an unequivocal identification of molecules with binding activity is possible. Normally, the selection of bound ligands is further facilitated in that the absolute intensity of transfer NOEs is much greater than that of NOEs of non‐binding molecules. In addition, transfer NOEs provide information on the three‐dimensional structure of the ligands in the bound state. Therefore, measuring transfer NOEs of mixtures of small molecules in the presence of large molecules, like proteins, should significantly enhance the options for screening mixtures of compounds for biological activity.