We have combined the pharmacological properties of the dynamin inhibitor dynasore with the photochromic properties of an azobenzene group, one of the best studied light-sensitive (photoswitchable) molecules.
Dr. Núria Camarero,
first co-author of the work.
Dynazos: the first inhibitors of endocytosis controlled by lightResearchers have used rational design to obtain the first light-regulated small-molecule inhibitor of endocytosis by a stepwise design to control dynamin. They characterized in detail the photochrome properties of dynazos under different light spectra and transient absorption spectroscopy and have obtained molecules that respond to violet visible light, what minimizes the potential negative effects of using UV light in living systems. Also, the biological activity of dynazos, at micromolar concentrations, was confirmed by confocal fluorescence microscopy, flow cytometry and Total Internal Reflection Microscopy (TIRFM) using different cell lines. The newly developed tool, that allows to turn on and off remotely and reversibly the biological activity of dynamin, will certainly be very relevant to decipher the role of endocytosis in cellular processes as cell growth, differentiation, motility and modulation of transmembrane receptor signalling and synaptic transmission, among others. Endocytic processes also can be targeted to prevent infections, avoiding the entering of pathogens, or to intentionally kill cells by the uptake of toxic compounds.
Dynazos technology opens the doors to use light as the external trigger to control drug’s pharmacologic activity affecting endocytosis processes with high spatiotemporal resolution.Reference article: Núria Camarero, Ana Trapero, Ariadna Pérez-Jiménez, Eric Macia, Alexandre Gomila-Juaneda, Andrés Martín-Quirós, Laura Nevola, Artur Llobet, Amadeu Llebaria, Jordi Hernando, Ernest Giralt, and Pau Gorostiza. Photoswitchable dynasore analogs to control endocytosis with light. Chem. Sci., 2020. This work was done in collaboration with: Institute for Advanced Chemistry of Catalonia (IQAC-CSIC), Institut de Pharmacologie Moléculaire et Cellulaire (IPMC), Institute for Research in Biomedicine (IRB Barcelona), Bellvitge Biomedical Research Institute (IDIBELL), Departament de Química, Universitat Autònoma de Barcelona (UAB), Universitat de Barcelona (UB). The “Nanoprobes and nanoswitches” group is part of the CIBER-BBN network.
Professor Pau Gorostiza,
lead author of the work.