Fragment screening
Find which fragments of a library bind a target, from one photo-CIDNP scan per sample.
The question it answers
Which compounds of my library bind my target, including the weak binders in the millimolar range that a fragment campaign starts from?
How it works
Light polarises the ligand only while it is free in solution. A ligand that binds the target loses part of its photo-CIDNP signal. Two spectra of the same ligand are compared, without and with the target. A drop in signal marks a binder.
ligand, light onligand + target, light on
Published figures
| Measurement | One scan of 2 to 5 s per sample |
| Ligand concentration | Down to 5 µM |
| Target concentration | 2 µM |
| Throughput | 1,500 samples per day, automated flow-through |
| Library | 212 photo-CIDNP-active fragments |
What you need
- A light-coupled NMR spectrometer.
- A photosensitiser. Fluorescein is the standard.
- A library of photo-CIDNP-active compounds.
- The target protein. No isotope labelling.
Limits
Only molecules that show photo-CIDNP give a signal. The database lists which ones do, and the prediction algorithms estimate it for new structures.
A ligand that does not polarise can still be studied in competition with one that does.