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Updated: May 8, 2026

Harnessing the Bioorthogonal Inverse Electron Demand Diels-Alder Cycloaddition for Pretargeted PET Imaging
Published on: February 3, 2015
trans-Cyclooctene--a stable, voracious dienophile for bioorthogonal labeling
Ramajeyam Selvaraj1, Joseph M Fox
1Brown Laboratories, Department of Chemistry and Biochemistry, University of Delaware, Newark, DE 19716, United States.
Abstract:
Discussed herein is the development and advancement of trans-cyclooctene as a tool for facilitating bioorthogonal labeling through reactions with s-tetrazines. While a number of strained alkenes have been shown to combine with tetrazines for applications in bioorthogonal labeling, trans-cyclooctene enables fastest reactivity at low concentration with rate constants in excess of k2=10(6) M(-1) s(-1). In the present article, we describe advances in computation and synthesis that have enabled applications in chemical biology and nuclear medicine.
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