Highly Stable Meldrum’s Acid Derivatives for Irreversible Aqueous Covalent Modification of Amines

This work describes the development of a highly stable and pH-responsive probe for lysine modification. The scaffold has marked stability in the presence of several biological nucleophiles and across a wide pH range (2–12). Several functional analogs showed robust labeling of a protein at pH > 9. Taken together, our system displays versatility and can be easily adapted for variety of applications, while demonstrating stability suitable for a wide range of biologically compatible systems.