10-23 DNAzyme has been used as a very good model for exploring the potential of functional nucleic acids. Its 15-mer catalytic core has been demonstrated to be the optimized in vitro selection result. However, with the introduction of protein-like functional groups through 2'-deoxyguanosine analogues, its two highly conserved guanine residues (G2 and G14) can be modified for more efficient 10-23 DNAzyme analogues. This result implies that chemical modifications of functional nucleic acids with well-designed nucleoside analogues of each canonical residue could be used as the first step in the efforts toward more powerful functions of nucleic acids.