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Developing bioorthogonal chemical reactions for improved drug delivery

A postgraduate research opportunity at the University of Otago.

Details

Close date
Saturday, 31 March 2018
Academic background
Sciences, Health Sciences
Host campus
Dunedin
On-campus or via distance?
On-campus
Qualification
PhD
Supervisor
Dr Allan Gamble

Overview

Projects for PhD candidates to work in the area of bioorthogonal chemistry are available. The goal of the research is to gain greater control and faster activation rates of bioorthogonal chemical reactions used for drug delivery. Design, synthesis, activation and biological evaluation of prodrugs, nanoparticles and imaging probes would be investigated.

Background

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, the proposed projects would look at taking advantage of a “click-and-release” type strategy for targeted and controlled prodrug, probe or nanoparticle 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 (see reference below). In a continuing effort, the successful candidate(s) will be investigating methods to improve our reaction for pre-clinical studies.

The project will involve the design and multi-step synthesis of small molecules or polymers using synthetic chemistry techniques such as anhydrous reaction conditions, column chromatography, HPLC purification, NMR, MS and IR characterisation. A research background in organic chemistry, medicinal chemistry or physical organic chemistry is essential. Full training in advanced synthetic chemistry techniques and cell biology will be provided throughout the project.

The work will be based in the School of Pharmacy.

Additional information

The candidate will hold a BSc (Hons) or MSc in organic or medicinal chemistry or synthetic drug discovery or a related discipline, or a BPharm (Hons) or MPharm with significant practical organic chemistry experience, and will be enthusiastic and passionate about research. A strong research background in organic chemistry would be highly desirable.

Reference: Matikonda, S. S.; Orsi, D. L.; Staudacher, V.; Jenkins, I. A.; Fiedler, F.; Chen, J.; Gamble, A. B. Bioorthogonal prodrug activation driven by a 1,3-dipolar cycloaddition. Chem. Sci. 2015, 6, 1212-1218.

Contact

Dr Allan Gamble
Tel   64 3 479 7324
Email   allan.gamble@otago.ac.nz