A Concise Synthetic Approach to Highly Reactive Click-to-Release Trans-Cyclooctene Linkers

27 December 2022, Version 1
This content is a preprint and has not undergone peer review at the time of posting.

Abstract

An increase of the click-to-release reaction rate between cleavable trans-cyclooctenes (TCO) and tetrazines would be beneficial for drug delivery applications. In this work, we 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 5-fold more reactive sTCO exhibited the same in vivo stability as the parent TCO linker when used as antibody linker in circulation in mice.

Keywords

Cleavage Reactions
Click Chemistry
Pyridazine Elimination
Tetrazine
Trans-Cyclooctene

Supplementary materials

Title
Description
Actions
Title
Supplementary Information
Description
Synthesis experimentals and methods for reactivity and release evaluations
Actions

Comments

Comments are not moderated before they are posted, but they can be removed by the site moderators if they are found to be in contravention of our Commenting Policy [opens in a new tab] - please read this policy before you post. Comments should be used for scholarly discussion of the content in question. You can find more information about how to use the commenting feature here [opens in a new tab] .
This site is protected by reCAPTCHA and the Google Privacy Policy [opens in a new tab] and Terms of Service [opens in a new tab] apply.