PHOTOACTIVATION/CELL BIOLOGY/THERAPY: Photo-switchable peptides promise precision control of drugs, and limited side effects

A newly developed class of photo-switchable molecules that enable remote, noninvasive control of protein-protein interactions will serve as a prototype to develop photo-switchable drugs with side effects limited by location and time.

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A newly developed class of photo-switchable molecules that enable remote, noninvasive control of protein-protein interactions will serve as a prototype to develop photo-switchable drugs with side effects limited by location and time.1

Dr. Ernest Giralt of the Design, Synthesis, and Structure of Peptides lab at Institute for Research in Biomedicine (IRB; Barcelona, Spain) led a team of researchers at two sites in Spain, and synthesized two peptides (small proteins) that change shape when illuminated. The peptides thereby allow or prevent specific protein-protein interactions. Such protein association is necessary for endocytosis, a process by which cells allow molecules to breach their protective membrane.

Photosensitive peptides allow the researchers to use focalized light "like a magic wand to control biological processes and to study them," says professor Pau Gorostiza, who heads the Nanoprobes and Nanoswitches lab at the Institute for Bioengineering of Catalonia (IBEC; also in Barcelona). IRB and IBEC researchers say these molecules have immediate use for studying in vitro endocytosis in cancer cells, and would allow selective control over proliferation of such cells.

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Photo-switchable peptides able to modulate biological processes are promising for research, treatment, and personalized medicine. (Image courtesy of Laura Nevola)

The peptides would also facilitate work in developmental biology, where cells require endocytosis to change shape and function—processes that are orchestrated with great spatial and temporal precision. In this application, they allow manipulation of complex development of a multicellular organism using light patterns. The researchers are now working on a general recipe to design photo-switchable inhibitory peptides that can be used to manipulate other protein-protein interactions inside cells by applying light.

Dr. Gorostiza had the idea to manipulate biological and pharmacological processes using light after working in this area at the University of California-Berkeley on two projects (OpticalBullet and Theralight) that involved collaboration with Giralt's lab. He says the most immediate therapeutic applications will probably be for diseases affecting superficial tissue such as the skin, the retina, and the most external mucosal membranes. The combination of drugs with external light control may contribute to the development of personalized medicine in which treatments can be adapted to each patient.

The researchers are now working to enhance the photochemical response of the compounds, and to enable stimulation at visible wavelengths. Furthermore, photo-conversion of the compounds needs to be improved, as does their stability in the dark.

1. L. Nevola, Angew. Chem. Int. Ed., doi:10.1002/anie.201303324 (2013).

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