Wednesday, 8 June 11:00am – 12:00pm

This seminar will be delivered in Chemistry Lecture Theatre 4 and Online Zoom Please email chemistry.researchsupport@sydney.edu.au for zoom link and password.

Speaker: Dr Oliver Thorn-Seshold; Ludwig Maximilian University of Munich

Host: Prof. Liz New

Title: High-resolution chemical probes for microtubules and oxidoreductases

Abstract: Our group builds rationally-designed chemical reagents for use in cellular and in vivo biology studies. This talk sketches recent progress in two tenuously-linked topic areas:

(1) Photoswitchable chemical reagents (photopharmaceuticals) are tools that can target protein inhibition to individual cells with millisecond temporal precision. In cytoskeleton research, this precision enables studies at previously impossible resolution. Recent developments of in vivo-competent cytoskeleton photopharmaceuticals will be shown: (i) metabolically robust, GFP-compatible photoswitches optimised as destabilisers for microtubule photocontrol in fly, fish, worm, frog, and mouse;^[1-3] (ii) taxane- and epothilone-based stabilisers with nanomolar potency and subcellular precision.^[4-5]

(2) The biochemical dynamics of redox in health and disease remain largely unknown, since we lack tools to image or harness redox turnover in cells. Dithiol oxidoreductases (A) are crucial targets that are hard to address selectively, as their chemistries are so similar. We design dichalcogenide probes using topologies and geometries that avoid kinetic liability,^[6] that can selectively probe e.g. the dithiol effector thioredoxin (Trx; B)^[7] or the selenolthiol thioredoxin reductase (TrxR; C)^[8]. These are now enabling high-throughput counterscreens for reductase inhibitors, and redox prodrug therapeutics (D).

All are welcome and tricky questions are particularly invited!

[1] Cell Chem Biol 2021, doi.org/f5qh; [2] Angewandte 2021, gs63; [3] JACS 2022, f4zt; [4] Nat Commun 2020, gnsd; [5] Angewandte 2022, g94z; [7] Nat Commun 2022, f4zw; [8] JACS 2021, gkbxdd; [9] Chem 2022, gmxm.