Antibody–Linker
Importance
- Determines the bio-conjugation method.
- Defines the drug-to-antibody ratio (DAR).
- Affects stability and off-target toxicity.
Challenges
- Retro-Michael exchange of maleimide can cause off-target toxicity.
- Heterogeneous DAR.
SmartLinker™ Platform
Solution: Design of novel linkers
SiMologics designs linkers that selectively bind to antibody-specific residues. They are engineered to overcome the stability, heterogeneity and off-target toxicity limitations of conventional ADC chemistries.
Anatomy of a conjugate
Three engineered segments connect the antibody to a cytotoxic payload or gold nanoparticle (GNP).
Linker Cleavability
Cleavable vs non-cleavable
Importance
- Determines cleavage method and payload conjugation strategy.
- Affects stability, off-target toxicity, hydrophilicity and ADME.
Challenges
- Undesired non-specific release of payload in normal tissues, leading to off-target toxicity.
Linker–Payload
Importance
- Determines the leaving group or linker.
- Defines payload species.
- Affects off-target toxicity, hydrophilicity and potency.
Challenges
- Rapid expansion of the payload arsenal means existing linker–payload attachments often fall short.
Endpoint optionsCytotoxic payloador Gold nanoparticles (GNPs)
The SiMologics linker
A linker that selectively binds to antibody-specific residues
- Stable under physiological conditions
- Site-selective: binds residues that don't interfere with antigen binding
- PEG-extended for enhanced solubility
- Compatible with GNPs and a range of cytotoxic payloads via two linking options
Interested in collaborating on ADCs or antibody–GNP conjugates?
We work with biotech, pharma and academic partners on linker design and conjugation programmes. We're always happy to provide advice on antibody conjugation strategies, from chemistry selection to DAR optimisation.