Nickel salts catalyze fast cysteine arylation with 2-nitroarylboronic acids. The process uses cheap, readily-available reagents and allows introduction of diverse chemical handles.

Side-chain modifications that respond to external stimuli provide a convenient approach to control macromolecular structure and function. Responsive modification of backbone amide structure represents a direct and powerful alternative to impact folding and function. Here, we describe a new photocaging method using histidine-directed backbone modification to selectively modify peptides and proteins at the amide N-H bond. A new vinylogous photocleavage method allows photorelease of the backbone modification and, with it, restoration of function.

Key Points Atovaquone induces AML blast apoptosis and prolongs survival in AML xenografts. Atovaquone induces proapoptotic signaling and inhibits the mTOR pathway through upregulation of ATF4 and also suppresses OXPHOS.

Photocaging groups provide spatiotemporal control of function. This review surveys approaches to the design and synthesis of photocaged peptides and proteins, and provides an overview of the ways in which these tools have been applied to answer biological questions.