|Project Members:||Polina Prokofeva, Guillaume Médard,|
What if we could establish, thanks to chemical proteomics, a simultaneous structure-affinity-relationship for all expected and unexpected targets of a class of molecules?
In this approach, the potential of each synthesized molecule is evaluated in an unbiased way using mass-spectrometry based chemical proteomics. All analogues are linkable molecules, which, once synthesized, are immobilized on a solid matrix to create as many affinity matrices. Comparison of the proteins enriched by these different matrices in pulldown experiments out of cell lysate should reveal in a unique way the structure affinity relationship of a class of molecules for the entire native proteome. In particular, the activity cliffs as well as the promiscuity cliffs of the pharmacophore will be evidenced.