TCO-PEG8-acid is a very reactive click chemistry reagent. The terminal carboxylic acid (CO2H) can react with primary amine groups in the presence of activators (e.g. EDC, or HATU) to form a stable bond. TCO moiety is reactive with tetrazine-containing compounds to form a stable bond without the catalysis of Cu or elevated temperatures. The inverse-electron demand Diels-Alder cycloaddition reaction of TCO with tetrazines is the fastest bioorthogonal reaction with exceptional selectivity. The hydrophilic PEG spacer increases solubility in aqueous media.