These results demonstrate that cathepsin B cleaves ODN4UV into T10phosphate and Val-Ala-T12. We further investigated the enzymatic cleavage kinetics of 2 M Val-Ala dipeptide in FAM-labeled ODN4UV by 0.2 U/mL cathepsin B, and found that almost all the dipeptide was cleaved within two hours (Figure ). Having confirmed the release of T10-phosphate from ODN4UV after enzymatic cleavage, we proceeded to construct oligonucleotide-small molecule conjugates with a cleavable dipeptide linkage. Various small molecules phosphoramidites can be quickly and efficiently attached to the Val-Ala(NB) linker and oligonucleotide sequences on a DNA synthesizer instead of resorting to complicated organic synthesis, and this is a key advantage of the automated modular synthesis. CA4 is a microtubule destabilizing small-molecule drug (Figure ), and its phosphate derivative is a prodrug which converts into dephosphorylated compound by intracellular phosphatase.