Catalytic Antibiotics: Targeted protein degraders based on terpene natural products.

The pursuit of new antibiotics is one of almost unparalleled importance, seeing as the death toll for infectious diseases continues to rise.

Traditional drug development based on small molecules has, however, not stood up well to this challenge as the emergence of multi-drug-resistant bacteria is causing these drugs to lose their effect.

Despite the evident need for new antibiotics, the pharmaceutical industry has largely abandoned this field due to the associated lower profits.Classical approaches to antibiotic drug design have been restricted to the reversible inhibition of a target bacterial protein.

Conversely, this proposal seeks to deviate conceptually from the way we approach antibacterial drug development and to instead establish means for the irreversible degradation of bacterial proteins, a concept that has not yet been applied to native bacterial proteins.By combining newly developed synthetic methodology with the forefront of chemical biology innovation, we aim to create bi-functional molecules that can hijack the bacteria’s endogenous protease system and target essential bacterial proteins for permanent degradation.Ultimately, we intend to develop a new class of antibacterial agents to combat multi-drug-resistant bacteria and to apply this novel technology to infectious diseases that are riddled with long drug treatments and drug resistance, such as tuberculosis.