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

• DOI: 10.1021/acs.orglett.0c00597
• Publication Date: 2020-03-19T19:54:10Z
• Authors: Garrett J. Davis; Holly A. Sofka; John C. Jewett
• Keywords: Dioxanes; Molecular Structure; Lysine; Water; Amines; Hydrogen-Ion Concentration; 01 natural sciences; 0104 chemical sciences

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.