TCO-PEG12-NHS ester | CAS 2185016-39-9

TCO-PEG12-NHS ester is a polyethylene glycol (PEG)–spaced trans-cyclooctene (TCO) click chemistry reagent designed for rapid bioorthogonal conjugation workflows. As an NHS ester, it reacts with primary amines on proteins, peptides, and other amine-bearing biomolecules to install the TCO handle for subsequent strain-promoted inverse electron-demand Diels–Alder (SPIEDAC) ligation. The extended PEG12 linker improves aqueous solubility and helps reduce steric constraints, making it a widely used building block for preparing TCO-functional probes, imaging reagents, and conjugatable biomaterials that require efficient downstream click coupling.

1. Protein Labeling And Targeting

TCO-PEG12-NHS ester is commonly used to functionalize antibodies, antibody fragments, and affinity ligands with a TCO handle for downstream click conjugation to complementary partners such as tetrazines. By coupling the NHS ester to lysine residues under standard bioconjugation conditions, researchers generate TCO-modified targeting constructs that can be assembled with imaging dyes, affinity tags, or multivalent scaffolds through fast bioorthogonal ligation. The PEG12 spacer helps maintain accessibility of the TCO moiety, which is particularly valuable when conjugates are prepared for sensitive binding assays, flow-based characterization, or modular probe assembly in research pipelines.

2. Molecular Imaging Probe Construction

TCO-PEG12-NHS ester supports the preparation of modular molecular imaging reagents by enabling controlled installation of TCO on carrier biomolecules prior to conjugation with tetrazine-bearing imaging reporters. In imaging reagent development, the PEG12 linker is frequently leveraged to improve handling in aqueous buffers and to reduce steric hindrance that can limit labeling efficiency of the click step. Teams building fluorescent, luminescent, or radiolabel-adjacent probes often use this reagent to create a consistent TCO density on protein scaffolds, facilitating reproducible downstream coupling to tetrazine-functional reporters for platform-style probe generation.

3. Diagnostic Reagent And Assay Platforms

TCO-PEG12-NHS ester is used in diagnostic reagent development to generate TCO-functional capture or detection components that can be rapidly coupled to tetrazine-modified assay reagents. The NHS-ester chemistry allows straightforward amine labeling of proteins used in immunoassays, binding assays, and bead-based detection formats, while the TCO handle enables subsequent click assembly without the need for additional catalysts. This approach is especially attractive for workflows that require modular reagent exchange, such as producing standardized conjugates for assay optimization, multiplexing strategies, or internal method development where rapid, orthogonal coupling is advantageous.

4. Surface And Biomaterial Functionalization

TCO-PEG12-NHS ester is applied to functionalize amine-present surfaces and biomaterial platforms, including polymeric materials, hydrogel components, and bead or particle systems bearing reactive amine groups. By installing TCO via NHS-ester coupling, researchers create materials that can be selectively decorated with tetrazine-tagged ligands, reporters, or crosslinking elements through SPIEDAC chemistry. The PEG12 spacer can improve presentation of the reactive TCO group at the material interface, supporting more reliable coupling and better accessibility for downstream functionalization steps used in materials research, biosensor development, and modular biomaterial assembly.