G4S linker

The poly-Glycine-Serine (G4S) linker is a type of flexible, unstructured synthetic peptide linker sequence often leveraged to connect the variable heavy (VH) domain and variable light (VL) domain of single-chain variable fragments (scFvs) and chimeric antigen receptors (CARs) that utilize an extracellular domain scFv for target antigen recognition. The linker itself consists of a core pentapeptide sequence, Gly-Gly-Gly-Gly-Ser, that is repeated and commonly found as either a 15-mer (G4S)3 or20-mer(G4S) 4 within scFv-based CARs and scFv fragments. The linker sequence length plays a role in controlling scFv stability and the noncovalent association between the VH and VL domains.