covalent handle

A unique set of molecules containing mild electrophilic moieties that covalently interact with amino acid residues in the target protein. The diversity of our compounds for covalent drug discovery ranges from natural product-like scaffolds to macrocycles, creating multiple opportunities in hit generation for a selected target.

Linkers, as key structural units in PROTAC molecules that connect the two functional ends, not only determine the overall molecular conformation and spatial compatibility but also directly influence the stability of the ternary complex, as well as cellular permeability and degradation efficiency. In recent years, with the widespread application of click chemistry in medicinal chemistry, the incorporation of bioorthogonal reactive groups such as azides (-N₃) into PROTAC linker design has become an emerging research focus, providing an important tool for modular assembly and rapid structural optimization.

The MCE Azide PROTAC Linker Library contains 190 linkers specifically designed for targeted protein degradation molecule design and optimization. These linkers serve as efficient “click handles,” enabling rapid and highly selective covalent coupling with alkyne reaction partners, thereby facilitating modular assembly and structural diversification of PROTAC molecules. In drug development, this design not only improves the efficiency of molecular construction but also significantly accelerates the screening and optimization of lead compounds. Meanwhile, by tuning linker properties such as length, flexibility, and polarity, the ability to form ternary complexes and degradation activity can be optimized.