As a class of protease-cleavable linkers, peptide linkers are an important component of antibody-drug conjugates (ADCs). Through chemical bonds, peptide linkers serve to connect active drugs to antibodies.

Background of Peptide Linkers

Through chemical links, ADCs could connect bioactive small molecule drugs to antibodies. As carriers, monoclonal antibodies are used to transport small molecule drugs to target cells. ADC drugs are composed of cytotoxic small molecule drugs, linkers and monoclonal antibodies. The main challenge of ADCs is determined by the linkers. Therefore, the overall success in developing effective, nontoxic and safe ADC drugs is to assemble an ideal chemical connector which links monoclonal antibodies and cytotoxic payload. Currently, there are two main types of ADCs linkers, cleavable linkers and non-cleavable linkers. As cleavable linkers, peptide linkers are characterized by blood flow stability and effectiveness in releasing intracellular payload.

Machine of Peptide Linkers

Peptide linkers are a kind of bridge between antibodies and toxic small molecules, which can be stable in vitro and circulatory system to avoid cytotoxicity caused by ADCs. When ADCs are internalized, peptide linkers can effectively disconnect and then release active small molecules. Small molecules diffuse to the action site and play an active role, so as to kill tumor cells.

Application of Peptide Linkers

ADC drugs containing peptide linkers could be used for anti-tumors. Peptide linkers use lysosomal proteases such as cathepsin B to recognize and cut off the connecting peptides to release drugs. For example, ADCs containing peptide linkers are stable in body fluid. After entering the target cells, they quickly digest and release auristatins (MMAEs) in the lysosome. MMAEs act on tubulin, thereby inhibiting tumor cell division and killing tumor cells.