A Concise Synthetic Approach to Highly Reactive Click‐to‐Release <i>Trans</i> ‐Cyclooctene Linkers**
Bing Liu, Wolter ten Hoeve, Ron M. Versteegen, Raffaella Rossin, Laurens H. J. Kleijn, Marc S. Robillard
Abstract
An increase in the click-to-release reaction rate between cleavable trans-cyclooctenes (TCO) and tetrazines would be beneficial for drug delivery applications. In this work, we have developed a short and stereoselective synthesis route towards highly reactive sTCOs that serve as cleavable linkers, affording quantitative tetrazine-triggered payload release. In addition, the fivefold more reactive sTCO exhibited the same in vivo stability as current TCO linkers when used as antibody linkers in circulation in mice.
Topics & Concepts
TetrazineClick chemistryCombinatorial chemistryChemistryBioorthogonal chemistryIn vivoStereoselectivityCycloocteneOrganic chemistryCatalysisBiologyBiotechnologyClick Chemistry and ApplicationsMonoclonal and Polyclonal Antibodies ResearchChemical Synthesis and Analysis