SAR by ILOEs: An NMR‐Based Approach to Reverse Chemical Genetics

Abstract
Reverse chemical genetics is an emerging technique that makes use of small molecule inhibitors to characterize how a protein functions. In this regard, we have developed an NMR‐based approach (SAR by ILOEs) that enables the identification of high affinity ligands for a given protein target without the need of a specific assay. Our approach is of general applicability and could result very powerful in reverse chemical‐genetics studies, target validation, and lead discovery. We report a recent application on the design and synthesis of compounds that inhibit protein‐membrane interactions.