TCO-C3-PEG3-C3-amine | CAS 2028288-77-7

TCO-C3-PEG3-C3-amine is a strained trans-cyclooctene (TCO) click chemistry reagent bearing a flexible PEG3 linker and a terminal primary amine. As a cycloaddition partner for tetrazine-mediated inverse electron-demand Diels–Alder reactions, it is widely used to introduce TCO handles onto biomolecules and surfaces while maintaining aqueous compatibility through PEG spacing. The included amine functionality enables straightforward downstream conjugation to activated esters, isothiocyanates, aldehydes, or other amine-reactive chemistries, supporting modular probe and material assembly for chemical biology and molecular imaging workflows.

1. Tetrazine Probe Conjugation

TCO-C3-PEG3-C3-amine is commonly used as the TCO-bearing component in tetrazine click labeling schemes, where TCO-functionalized targets are reacted with tetrazine-functional probes to generate stable conjugates under mild conditions. Researchers use this format to build libraries of imaging and detection reagents by first installing the TCO handle on a carrier (such as a peptide, protein, or polymer) and then performing the final conjugation step with a tetrazine probe. The PEG3 spacer and the amine-bearing tail help reduce steric constraints and improve practical conjugation handling in aqueous buffers, which is particularly valuable when preparing multicomponent constructs for microscopy, flow-based assays, or analytical characterization.

2. Surface And Material Functionalization

TCO-C3-PEG3-C3-amine is well suited for introducing reactive TCO groups onto material surfaces and biomaterial scaffolds that are subsequently labeled with tetrazine-tagged reporters. The terminal amine supports coupling to surface chemistries such as activated carboxylates or aldehyde-based linkers, enabling covalent immobilization of TCO functionality on nanoparticles, hydrogels, or functionalized membranes. This application is frequently adopted in materials science and chemical biology to create spatially addressable or batch-labeled platforms, where the TCO handle serves as a modular attachment point for fluorescent dyes, affinity tags, or other tetrazine-reactive components used to track binding, distribution, or surface interactions.

3. Bioconjugation Building Block Chemistry

TCO-C3-PEG3-C3-amine functions as a versatile bioconjugation building block for constructing multi-functional biomolecular reagents that require both a click handle and a reactive handle for additional coupling. The primary amine enables attachment to a wide range of amine-reactive partners, allowing users to generate TCO-containing conjugates with controlled stoichiometry and adaptable labeling strategies. In research settings, this reagent is often employed to prepare TCO-modified ligands, affinity reagents, or carrier scaffolds that can later be combined with tetrazine-functional components to yield final probe architectures for mechanistic studies, target engagement mapping, or workflow-compatible reagent assembly.

4. Fluorescent And Affinity Tag Labeling

TCO-C3-PEG3-C3-amine is frequently used to incorporate TCO into fluorescent labeling and affinity-tagging workflows, where tetrazine-bearing dyes or binding modules are used to generate final conjugates. The PEG3 linker helps maintain probe accessibility, which is important for attaching imaging reporters to bulky biomolecular targets or densely functionalized surfaces. The amine functionality further supports pre-labeling strategies, such as coupling the reagent to carrier proteins or scaffold molecules prior to the tetrazine click step, enabling users to tailor labeling density and preserve binding-site availability in probe design for advanced analytical and imaging applications.