# Site-specific conjugation & linker chemistry

Source: https://nuclide.cc/technologies/site-specific-conjugation/  
Nuclide record `site-specific-conjugation` (Technology). Data CC BY-NC 4.0, attribute "Data from Nuclide (nuclide.cc)"; commercial use needs a licence.

## TL;DR

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.

## Fields

- Kind: Technology
- Status: established
- Last checked: 2026-09-04
- 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

## Sources

- Wikipedia: https://en.wikipedia.org/wiki/Bioconjugation
- Wikipedia: https://en.wikipedia.org/wiki/Bioconjugation

## Connected records

- indications: [HER2-positive breast cancer](https://nuclide.cc/indications/breast-her2-positive/)
- fronts: [Radiochemistry & manufacturing](https://nuclide.cc/fronts/f-radiochemistry/)
- terms: [Chelator (bifunctional chelating agent)](https://nuclide.cc/terms/chelator-term/)

---
JSON: https://nuclide.cc/api/v1/entities/site-specific-conjugation.json