Seminar: Dr Allan Gamble - The Need for Speed: Bioorthogonal Prodrug Activation using Click-Chemistry

Tuesday, 1 August 2017 - 12:00pm – Tuesday, 1 August 2017 - 1:00pm  |  Chem Sci M11

Speaker: Dr Allan Gamble

Bioorthogonal chemical reactions (chemical reactions performed in a living system) have been utilised in bioconjugation and imaging strategies. While these reactions could be considered as “click-and-stick” type reactions, our group is interested in taking advantage of a “click-and-release” type strategy for targeted and controlled prodrug activation. To achieve sufficient prodrug activation in vivo, the reaction must be fast and the drug must be released in a high enough concentration to exert its biological response. We have identified a new and general bioorthogonal prodrug activation strategy based on the 1,3-dipolar cycloaddition of an azide and trans-cyclooctene. The bioorthogonal reaction (first step) is fast, but in some instances the rate of drug release (second step) is extremely slow. In this presentation I will discuss our in vitro proof-of-concept studies demonstrating how we have increased the rate of our bioorthogonal reaction. Mechanistic studies into how the drug is subsequently released will also be discussed. Taken together, the data provides insight into future prodrug development.