TCO PEG linkers (reagents) are a class of PEG linkers with PEG attached to a TCO group (trans-cycloctene), TCO reagent is highly reactive with tetrazine in an inverse electron demand Diels Alder (IEDDA) reaction followed by a retro-Diels Alder reaction to eliminate nitrogen gas. This is a fast reaction with a second order rate constant of 2000 M 1 s 1 (in 9:1 methanol/water) allowing modification of biomolecules at very low concentrations. Reactions have also been performed using TCO or norbornenes as dienophiles at second order rates on the order of 1 M 1 s 1 in aqueous media. This reaction has been applied in labeling live cells, molecular imaging and other bioconjugation applications.