Branched Linkers for Antibody-Drug Conjugates
Author Information
Author(s): Gulyak Evgeny L., Komarova Olga A., Prokopenko Yury A., Faizullina Elina A., Malabuiok Diana M., Ibragimova Aigul R., Mokrushina Yuliana A., Serova Oxana V., Popova Galina P., Zhitlov Mikhail Y., Nikitin Timofei D., Brylev Vladimir A., Ustinov Alexey V., Alferova Vera A., Korshun Vladimir A., Smirnov Ivan V., Terekhov Stanislav S., Sapozhnikova Ksenia A.
Primary Institution: Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Moscow, Russia
Hypothesis
The length of branched linkers affects the cytotoxic activity of antibody-drug conjugates (ADCs).
Conclusion
The study found that the length of the branched linker critically affects the cytotoxic activity of ADCs, with longer linkers showing better efficacy.
Supporting Evidence
- The study synthesized two branched linkers with different lengths and tested their effects on ADC activity.
- Longer branched linkers resulted in higher cytotoxicity compared to shorter ones.
- All ADCs maintained their affinity for the HER2 target despite differences in cytotoxicity.
Takeaway
This study shows that how long the connector is between the drug and the antibody matters a lot; longer connectors help the drug work better.
Methodology
The study synthesized branched amino triazide linkers and conjugated them to trastuzumab using an enzymatic method, followed by testing the resulting ADCs for cytotoxicity.
Limitations
The study did not explore all possible linker structures or their effects on ADC activity.
Digital Object Identifier (DOI)
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