{"entity":{"id":"site-specific-conjugation","kind":"technology","name":"Site-specific conjugation & linker chemistry","aka":[],"tldr":"Site-specific conjugation and linker chemistry decide exactly where and how many payloads attach to the antibody, which determines how safe and effective an ADC is.","summary":"Random lysine or cysteine conjugation (T-DM1, brentuximab) gives heterogeneous mixtures. Engineered cysteines (THIOMAB), glycan remodelling (Synaffix GlycoConnect), enzymatic (sortase, transglutaminase), and non-natural amino acids (Ambrx, Sutro) yield homogeneous DAR. Hydrophilic linkers (Mersana Dolaflexin, Zymeworks ZD06519 platform, MediLink TMALIN) allow DAR 8 without aggregation; cleavable tetrapeptide GGFG (DXd) versus non-cleavable SMCC (T-DM1) governs bystander effect.","status":"established","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/Bioconjugation","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Bioconjugation"}],"tags":[],"related":[],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Defined attachment sites and linker hydrophilicity control pharmacokinetics, aggregation, and payload release.","strengths":["Homogeneous product, better PK","Enables high DAR and dual payloads"],"limitations":["Manufacturing complexity"]},"route":"/technologies/site-specific-conjugation/","neighbours":{"indication":[{"id":"breast-her2-positive","kind":"indication","name":"HER2-positive breast cancer","route":"/indications/breast-her2-positive/"}],"section":[{"id":"f-radiochemistry","kind":"section","name":"Radiochemistry & manufacturing","route":"/fronts/f-radiochemistry/"}],"term":[{"id":"chelator-term","kind":"term","name":"Chelator (bifunctional chelating agent)","route":"/terms/chelator-term/"}]}}