After transfection, we found a clear decline of cell viability which can be attribute to the release of CA4 via intracellular cathepsin B-mediated cleavage of the dipeptide. In addition, payloads containing an amino group can conjugate with Val-Ala(NB) via a carbamate linkage through a two-step solidphase process, expanding the general utility of Val-Ala(NB) phosphoramidite in the facile synthesis of oligonucleotide-small molecule conjugates.