Methyltetrazine-activated biotinylation reagent that reacts with TCO-containing compounds via a Inverse-Electron-Demand Diels-Alder reaction to form a stable covalent bond and does not require Cu-catalyst or elevated temperatures. The inverse-electron demand Diels-Alder cycloaddition reaction of TCO with tetrazines is a bioorthogonal reaction that possesses exceptional kinetics (k > 800 ^-1 s^-1) and selectivity. Such excellent reaction rate constants are unparalleled by any other bioorthogonal reaction pair described to date.