Postgraduate Seminar: Marcus Graziotto
Wednesday, 28 October 2020. 11am – 12pm.
This seminar will be delivered via Zoom – Please email firstname.lastname@example.org for zoom link and password.
Marcus Graziotto, PhD Candidate, School of Chemistry.
Host: Assoc Prof Liz New
Functionalisable naphthalimide tetrazines for live cell imaging
Of the many chemical environments, the mitochondria, which are responsible for cellular metabolism, are worth investigation. These organelles possess a highly negative membrane potential which is indicative of cellular health. Thus, a new highly sensitive probe for the mitochondrial membrane potential (MMP) would be ideal for the monitoring of the changes in cellular health in response to a treatment.
In this talk, I will present the development of a fluorogenic probe for the MMP.1 First, a series of new naphthalimide tetrazines for fluorogenic click chemistry were synthesised. These molecules were fluorogenic and only fluoresce after reaction with a selective click partner. Photophysical analysis, computer modelling, and biological screening was used to identify the best probe design. Modifying both the naphthalimide tetrazine and click partner to incorporate mitochondrial targeting groups afforded a two-component probe. Each part of the probe is quenched until they meet and undergo click chemistry inside the mitochondria. The rate of click reaction and intensity of fluorescence is dependent on the MMP. We have instigated preliminary investigations as to how cells respond to cancer chemotherapy treatments using this probe.
- Graziotto M., New, E.; Probes for mitochondrial membrane imaging, 2020. Australian Patent Application 2020903689.