Ligands From Nothing

Well, nearly nothing. That's the promise of a technique that's been published by the Ernst lab from the University of Basel. They first wrote about this in 2010, in a paper looking for ligands to the myelin-associated glycoprotein (MAG). That doesn't sound much like a traditional drug target, and so it isn't. It's part of a group of immunoglobulin-like lectins, and they bind things like sialic acids and gangliosides, and they don't seem to bind them very tightly, either. One of these sialic acids was used as their starting point, even though its affinity is only 137 micromolar. They took this structure and hung a spin label off it, with a short chain spacer. The NMR-savvy among you will already see an application of Wolfgang Jahnke's spin-label screening idea (SLAPSTIC) coming. That's based on the effect of an unpaired electron in NMR spectra - it messes with the relaxation time of protons in the vicinity, and this can be used to determine whatever might be nearby. With the right pulse sequence, you can easily detect any protons on any other molecules or residues out to about 15 or 20 Angstroms from the spin label. Jahnke's group at Novartis attached spin labels to proteins and used these the find ligands by NMR screening. The NMR field has a traditional bias towards bizarre acronyms, which sometimes calls for ignoring a word or two, so SLAPSTIC stands for "Spin Labels Attached to Protein Side chains as a Tool to identify Interacting Compounds". Ernst's team took their cue ...
Source: In the Pipeline - Category: Chemists Tags: Drug Assays Source Type: blogs