Appendage and Scaffold Diverse Fully Functionalized Small-Molecule Probes via a Minimalist Terminal Alkyne-Aliphatic Diazirine Isocyanide

This paper highlights a bifunctional isocyanide that contains a photoreactive aliphatic diazirine for protein target capture and a terminal alkyne for click chemistry-based proteomics. Specifically, this isocyanide was employed in five different multicomponent reactions to produce 10 different fully functionalized small-molecule probes (FFSMPs) containing eight different chemical scaffolds. We anticipate this bifunctional isocyanide can be used to create FFSMP libraries of much greater chemical diversity toward identifying compounds with novel mechanisms of action via integrated phenotypic screening and target identification.