Using SPR to Characterize the Binding Modes of PROTAC Molecules

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PROteolysis-TArgeting Chimeras (PROTACs) are an exciting new development in drug discovery that have the potential to modulate protein targets once considered ‘undruggable’.

A small molecule is designed with two “warheads”, one binds to the protein target of interest (TOI) and the second binds to an E3 ligase such as VHL (right). The two are joined by a flexible linker which allows the E3 ligase to ubiquitinate the TOI – targeting it for degradation by the intracellular ubiquitin proteasome system.

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