Description:
Reference #: 1685
The University of South Carolina is offering licensing opportunities for Cyclopropanol as a bioorthogonal warhead for electrochemically controlled bioconjugation applications.
Background:
Bioconjugation techniques play an important role in modern chemical biology and biomedical sciences, such as protein drug stabilization, target therapy, and the development of antibody-drug conjugates, etc. Typically, biorthogonality is required for an effective in situ bioconjugation reaction, which enables the selective and non-disruptive labeling and manipulation of biomolecules within complex living systems. On the other hand, the size of the linker group, also termed as bioconjugation warhead, should be small enough to minimize the perturbation of biological processes. Therefore, azide, alkyne, diazirine, cyclopropene, and oxaziridine derivatives, have been widely used in bioconjugation reactions due to their bioorthogonal reactivities and small functional group size. While the reigning of click chemistry has boosted the application of azides and alkynes, making them the most popular molecules for bioconjugation applications, three-member ring systems have emerged as another type of powerful warhead in recent years.
Invention Description:
A novel and effective chemistry has been developed to provide a warhead for both in vitro and in vivo bioconjugation. Under mild electrochemical conditions, the invented warhead has a controllable reactivity yielding functionalities through the generation of radicals. The resultant products are amenable to reaction with other nucleophilic partners.
Potential Applications:
Protein drug stabilization, target therapy, and antibody-drug conjugates
Advantages and Benefits:
Biomolecules like peptides, proteins, and viruses could be effectively modified using warhead-derivatives under electrochemical conditions. Furthermore, integration of the warhead analog into living cells has been achieved via metabolic pathways, which could be subsequently activated under electrochemical conditions in situ. Consequently, labeling with hydrazide probes facilitates real-time visualization of phospholipids within a living organism, thereby attesting to the method's potential and versatility.