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

Bing Liu, Wolter ten Hoeve, Ron M. Versteegen, Raffaella Rossin, Laurens H.J. Kleijn, Marc S. Robillard (Corresponding author)

Research output: Contribution to journalArticleAcademicpeer-review

2 Citations (Scopus)

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.

Original languageEnglish
Article numbere202300755
Number of pages5
JournalChemistry - A European Journal
Volume29
Issue number45
DOIs
Publication statusPublished - 10 Aug 2023
Externally publishedYes

Keywords

  • cleavable linkers
  • click chemistry
  • iodolactonization
  • pyridazine elimination
  • trans-cyclooctene
  • Animals
  • Cyclooctanes/chemistry
  • Mice
  • Drug Delivery Systems

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