A novel method to incorporate an ultra-potent natural drug – duocarmycin – into an antibody-drug conjugate using solid-phase synthetic methods. Incorporating this ultra-potent drug using simple synthetic methods offers new therapeutic pathways for cancer drug delivery.


  • increased cell specificity
  • ease of synthesis
  • use of ultra-potent small drug molecules
  • potential to use many different drugs and proteins.

Antibodies can specifically target cancerous cells but tend to lack the appropriate level of cytotoxicity required to cause cell death. Small molecule drugs, however, are cytotoxic enough but also target noncancerous cells that divide rapidly, leading to side-effects such as vomiting, hair loss and throat ulcers.

Antibody-drug conjugates have the potential to offer cell specificity as well as high cytotoxicity. Composed of three subunits – a cytotoxic drug linked to an antibody by a biodegradable linker – the antibody-drug conjugate can deliver the cytotoxic drug to the cancerous cell, before the linker is broken and the drug is released, leading to cell death.

One problem currently facing antibody-drug conjugate production is the ease of synthesis, with many pathways not being able to control the amount of drug and the position of the linker. This innovation overcomes this issue and also allows for ultra-potent drugs to be used due to the specificity of their delivery into cancerous cells. This innovation also affords a straight forward synthesis using Fmoc-based solid-phase peptide methods.



J. Org. Chem. 2015, 80(19), 9454−9467. doi:10.1021/acs.joc.5b01373



Patent granted in the US US9765077.


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