Dde Biotin-PEG4-Picolyl azide is a cleavable reagent containing a biotin moiety and a picolyl azide moiety which can be conjugated with alkyne-containing biomolecules. This biotin reagent incorporates a copper-chelating motif that dramatically accelerates the Cu(I)-catalyzed Click Chemistry. The hydrophilic spacer arm provides better solubility to the labeled molecules in aqueous media. Dde protecting group allows efficient release of captured biotinylated molecules from streptavidin under mild conditions with hydrazine.