Antibody-drug conjugates charged with unconventional payloads

Antibody-drug conjugates (ADCs) represent one of the most advanced selective therapy that have attracted a lot of interest in recent years. ADCs consist of monoclonal antibodies (mAbs) that are bound to bioactive molecules (payloads) through specific linkers. The linker is one of the most important part of ADC due to its ability to stabilize the conjugates in the bloodstream, enhance the solubility of the ADC, prevent non-specific release of payload and finally release the bioactive compound in the target cell. ADCs are effective systems for target therapy in particular in treatment of cancer but also for bacterial infections resistant to conventional antibiotics. Less explored are the use of these systems for the treatment of viral infections. In this thesis, various linkers suitable for the bioconjugation of several payloads were synthesized and conjugated with mAbs to make novel ADCs for the treatment of cancer, bacterial and viral infections. The other part of the thesis was made in collaboration with a leading Italian pharmaceutical company. In this context, new synthetic strategies were explored for the preparation of intermediates useful for the synthesis of biological active compounds.