Bioorthogonal Removal of 3-Isocyanopropyl Groups Enables the Controlled Release of Fluorophores and Drugs in Vivo

2018/06/21 by Julian Tu, Minghao Xu, Saba Parvez +2 · 166 citations
Biochemistry, Genetics and Molecular Biology · Chemistry · #Advanced biosensing and bioanalysis techniques #Bioorthogonal chemistry #Biophysics #Chemical Synthesis and Analysis #Chemistry #Click Chemistry and Applications #Click chemistry #Combinatorial chemistry #Drug delivery #Fluorescence #Fluorophore #In vivo #Organic chemistry #Tetrazine

paper · doi:10.1021/jacs.8b05093

published in Journal of the American Chemical Society 140(27), 8410-8414 (American Chemical Society)

openalex publication_date 2018/06/21 · openalex created_date 2025/10/10 · openalex updated_date 2026/07/26

Abstract

Dissociative bioorthogonal reactions allow for chemically controlling the release of bioactive agents and reporter probes. Here we describe 3-isocyanopropyl substituents as masking groups that can be effectively removed in biological systems. 3-Isocyanopropyl derivatives react with tetrazines to afford 3-oxopropyl groups that eliminate diverse functionalities. The study shows that the reaction is rapid and can liberate phenols and amines near-quantitatively under physiological conditions. The reaction is compatible with living organisms as demonstrated by the release of a resorufin fluorophore and a mexiletine drug in zebrafish embryos implanted with tetrazine-modified beads. The combined benefits of synthetic ease, rapid kinetics, diversity of leaving groups, high release yields, and structural compactness, make 3-isocyanopropyl derivatives attractive chemical caging moieties for uses in chemical biology and drug delivery.

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