Peptides are well suited for use as tool compounds to interrogate biological systems and processes due to their chameleonic ability to mimic a potential protein partner within the biological system of interest. Their use in this application continues to grow as the rules governing permeability across the plasma membrane are further elucidated. Unfortunately, a well-defined secondary structure is often required for productive interaction with the other protein partners within the system of interest. Many covalent stapling methods have been introduced that stabilize and rigidify secondary structures within short peptide sequences since the pioneering working was published by Miller, Blackwell, and Grubbs. The most popular of strategy involves a cross coupling reaction between two unnatural amino acids bearing an alkenyl side chain, mediated by a 1st Generation Grubbs ruthenium catalyst. Herein, we present work further optimizing the ring closing metathesis reaction for expedient use, toward an end goal of fully automating both the synthesis and ring-closing metathesis reactions.
Literature number: P215