{"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":[],"cancers":[],"sections":["adcs","drug-discovery"],"technologies":["adc"],"targets":[],"drugs":[],"companies":["tubulis","enlaza-therapeutics"],"institutions":[],"pathways":[],"terms":["dar","linker"],"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":{"section":[{"id":"adcs","kind":"section","name":"Antibody-Drug Conjugates","route":"/fronts/adcs/"},{"id":"drug-discovery","kind":"section","name":"Drug Discovery Platforms","route":"/fronts/drug-discovery/"}],"technology":[{"id":"adc-cdmo-manufacturing","kind":"technology","name":"ADC bioconjugation manufacturing (CDMOs)","route":"/technologies/adc-cdmo-manufacturing/"},{"id":"adc","kind":"technology","name":"Antibody-drug conjugate (ADC)","route":"/technologies/adc/"},{"id":"antibody-oligonucleotide-conjugates","kind":"technology","name":"Antibody-oligonucleotide conjugates","route":"/technologies/antibody-oligonucleotide-conjugates/"},{"id":"dual-payload-adc","kind":"technology","name":"Dual-payload ADC","route":"/technologies/dual-payload-adc/"},{"id":"adc-supply-chain","kind":"technology","name":"The ADC supply chain (antibody, payload-linker, conjugation, fill)","route":"/technologies/adc-supply-chain/"}],"company":[{"id":"abzena","kind":"company","name":"Abzena","route":"/companies/abzena/"},{"id":"araris","kind":"company","name":"Araris Biotech (Taiho)","route":"/companies/araris/"},{"id":"enlaza-therapeutics","kind":"company","name":"Enlaza Therapeutics","route":"/companies/enlaza-therapeutics/"},{"id":"sutro-biopharma","kind":"company","name":"Sutro Biopharma","route":"/companies/sutro-biopharma/"},{"id":"synaffix","kind":"company","name":"Synaffix (Lonza)","route":"/companies/synaffix/"},{"id":"tubulis","kind":"company","name":"Tubulis (Gilead)","route":"/companies/tubulis/"}],"term":[{"id":"dar","kind":"term","name":"Drug-to-antibody ratio (DAR)","route":"/terms/dar/"},{"id":"linker","kind":"term","name":"Linker (ADC)","route":"/terms/linker/"}],"cancer":[{"id":"breast-her2-positive","kind":"cancer","name":"HER2-positive breast cancer","route":"/cancers/breast-her2-positive/"}],"trial":[{"id":"ace-breast-02","kind":"trial","name":"ACE-Breast-02","route":"/trials/ace-breast-02/"},{"id":"nct04829604","kind":"trial","name":"ARX788 in HER2-positive, Metastatic Breast Cancer Subjects (ACE-Breast-03)","route":"/trials/nct04829604/"}],"drug":[{"id":"arx788","kind":"drug","name":"ARX788","route":"/drugs/arx788/"},{"id":"luveltamab-tazevibulin","kind":"drug","name":"Luveltamab tazevibulin","route":"/drugs/luveltamab-tazevibulin/"}],"roadmap":[{"id":"adc-generations","kind":"roadmap","name":"ADC roadmap: from Mylotarg to bispecific and dual-payload ADCs","route":"/roadmaps/adc-generations/"}],"idea":[{"id":"idea-fund-academic-adc-bispecific-platform","kind":"idea","name":"An open engineering platform for academic ADCs and bispecifics","route":"/ideas/idea-fund-academic-adc-bispecific-platform/"},{"id":"idea-dual-payload-first","kind":"idea","name":"Dual-payload ADCs in first line to prevent resistance","route":"/ideas/idea-dual-payload-first/"},{"id":"idea-reg-adc-platform-designation","kind":"idea","name":"Platform designation for ADC linker-payloads so manufacturing data carry across","route":"/ideas/idea-reg-adc-platform-designation/"}]}}