PUBLICATION
Bioorthogonal Removal of 3-Isocyanopropyl Groups Enables the Controlled Release of Fluorophores and Drugs in Vivo
- Authors
- Tu, J., Xu, M., Parvez, S., Peterson, R.T., Franzini, R.M.
- ID
- ZDB-PUB-180622-41
- Date
- 2018
- Source
- Journal of the American Chemical Society 140(27): 8410-8414 (Journal)
- Registered Authors
- Peterson, Randall
- Keywords
- none
- MeSH Terms
-
- Animals
- Anti-Arrhythmia Agents/administration & dosage*
- Anti-Arrhythmia Agents/pharmacokinetics
- Delayed-Action Preparations/chemistry*
- Drug Liberation
- Fluorescent Dyes/administration & dosage*
- Fluorescent Dyes/pharmacokinetics
- Isocyanates/chemistry
- Mexiletine/administration & dosage*
- Mexiletine/pharmacokinetics
- Oxazines/administration & dosage*
- Oxazines/pharmacokinetics
- Zebrafish/embryology
- PubMed
- 29927585 Full text @ J. Am. Chem. Soc.
Citation
Tu, J., Xu, M., Parvez, S., Peterson, R.T., Franzini, R.M. (2018) Bioorthogonal Removal of 3-Isocyanopropyl Groups Enables the Controlled Release of Fluorophores and Drugs in Vivo. Journal of the American Chemical Society. 140(27):8410-8414.
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping