Herein, therefore, we overcome this problem by developing a novel dipeptide linker phosphoramidite for the automated and modular synthesis of oligonucleotide-small molecule conjugates. As shown in Figure , we synthesized Val-Ala(NB) dipeptide phosphoramidite in which the dipeptide is protected by a photolabile 2-nitrobenzyl group to enhance stability during DNA synthesis. After DNA synthesis, deprotection and photolysis, cathepsin B is able to cleave the Val-Ala dipeptide of oligonucleotide-payload conjugates. As a result, payload-phosphate is released which is further converted to the dephosphorylated small molecule by phosphatase enzymes. ODN7UV, a DNA conjugate with the microtubule destabilizing reagent combretastatin A-4 (CA4) attached via Val-Ala linker, was delivered to HCT116 cells by lipofectamine.