Could one manipulate nanoscale building blocks using chemical reactions like molecular synthesis to yield new supra-nanoscale objects? The precise control over the final architecture might be challenging due to the size mismatch of molecularly scaled reactive functional groups and nanoscale building blocks, which limits a control over the valence and specific locations of reaction spots. Taking advantage of programmable octahedral DNA frame, we report a facile approach of engineering chemical reactions between nanoscale building blocks toward formation of controlled nanoarchitectures. Azide and alkyne moieties were specifically anchored onto desired vertices of DNA frames, providing chemically reactive nanoconstructs with directionally defined valence. Akin to the conventional molecular reactions, the formation of a variety of nanoscale architectures was readily achieved upon mixing of the frames with the different reactive valence and at different stoichiometric ratios. This strategy may open a door for a programmable synthesis of supra-nanoscale structures with complex architectures and diversified functions.