Figure 1.
Towards microtubule stabiliser photopharmacology. a) α/β‐Tubulin heterodimer with drug binding sites, [9] and major MT photopharmaceutical chemotypes. b) Epothilone binding to β‐tubulin induces the M‐loop to fold into a helix and repositions it to stabilise tubulin–tubulin lateral contacts, so stabilising the MT. A key interaction is the H‐bond from Thr276 to the thiazole nitrogen (adapted from PDB 4o4i [26] ). c) Synthesis and cellular evaluation of photoswitchable SBT‐derivatised taxane SBTax. d) Epothilones. The epoxide of EpoA/B is dispensable (EpoC/D). e) Designs for peripherally attaching the styrylthiazole (ST) photoswitch to epothilone: intending to photoswitchably induce and position the M‐loop helix, and/or change binding affinity, and/or reposition an H‐bond acceptor.