Many small-molecule drug candidates fail to advance since their poor pharmacokinetics or unmanageable toxicities. One method to overcome these barriers is to covalently conjugate small-molecule drugs with targeting ligands for targeted delivery. There are examples of ADCs, aptamer-drug conjugates (ApDCs) and small molecule-drug conjugates (SMDCs). By using of Val-Ala(NB) monomer and DNA synthesizer, sgc8-CA4, GalNAc-CA4 and NH2-DNA-CA4 conjugates are readily obtained (Figure ). NH2-DNA-CA4 conjugate contains an active amino group which are able to connect with antibody via crosslinker to synthesize ADCs (Figure ). These results suggest the promising of Val-Ala(NB) in the development of various of targeting ligands-drug conjugates. The attachment of small molecules to oligonucleotides via the Val-Ala(NB) linker reported in this work is modular and automated. This means any functional small molecule phosphoramidite can be quickly and efficiently conjugated to oligonucleotides via the Val-Ala(NB) linker on a DNA synthesizer, instead of resorting to complex organic synthesis. In addition, solid-phase conjugation of small molecules containing amino group with the Val-Ala(NB) linker through a carbamate linkage was achieved, expanding the general utility of this dipeptide in the construction of oligonucleotide-small molecule conjugates.