The reversible regulation of the cellular enzymes can have profound importance in biology, and may be used to tune the activity of over-expressed proteins in cancer cells. In order to explore this area, we have targeted carbonic anhydrase, a zinc containing metalloenzyme that is overexpressed in hypoxic cancer cells. This overexpression leads to a pH imbalance in tumors and provides a positive pathway for the metastasis. For that purpose, we have designed photoisomerizable azobenzene-based inhibitors that can isomerize between two isoforms, with only one form inhibiting the protein. This isomerization process is achieved by light, which makes it suitable for non-invasive cellular enzymes regulation in live biological systems. The focus of the talk will be the strategy behind the design in terms of visible light isomerization, long lifetime and high stability of each isomer. In addition, the effect of these molecules on the intracellular pH of cancer cells will be discussed.

Photoswitchable probes to reversibly control the activity of carbonic anhydrase in cancer cells

255th National Meeting (2018)

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