Breakthrough enables photosensitive-drug development
BARCELONA, Spain – A chemical nano-engineering breakthrough favoring the development of light-regulated therapeutic molecules could lead to personalized medicine that limits treatment time and reduces unwanted results.
Modifying biological processes with light has led to new fields of research, such as optogenetics and optopharmacology, and to the development of numerous tools for biology and medicine. Combining drugs with external devices to control light could enable the development of photosensitive drugs, but researchers must enhance the photochemical response of the compounds and be able to stimulate them at visible wavelengths for this to work.
“Prolonged illumination with ultra-violet light is toxic for cells and is therefore a clear limitation as well as having little tissue penetration capacity,” said Dr. Ernest Giralt of the Institute for Research in Biomedicine (IRB Barcelona).
Researchers at IRB Barcelona and IBEC design the first peptides regulated by light to modulate biological processes. Courtesy of Laura Nevola.
Additionally, the photoconversion of the compounds needs to be improved, as does their stability in the dark, to be able to “on demand, design them in such a way that they relax rapidly when irradiation with light stops, or that they ‘remember’ for hours or days the light stimulation received,” added Pau Gorostiza, ICREA professor and head of the Nanoprobes and Nanoswitches Lab at the Institute for Bioengineering of Catalonia (IBEC).
Giralt, Gorostiza and colleagues synthesized two peptides that, upon irradiation with light, change shape, allowing or preventing a specific protein-protein interaction. The association of these two proteins is required for endocytosis, a process in which cells allow molecules to penetrate the cell membrane. Postdoc Laura Nevola and doctoral student Andrés Martín-Quirós have spent the past four years working on the design of these photosensitive peptides.
“Photosensitive peptides act like traffic lights and can be made to give a green or red light for cell endocytosis,” Giralt said. “They are powerful tools for cell biology.”
“These molecules allow us to use focalized light like a magic wand to control biological processes and to study them,” Gorostiza said.
The molecules could be used for in vitro endocytosis in cancer cells, where this process is uncontrolled, allowing selective inhibition of the proliferation of these cells. They also could enable the study of developmental biology – where cells require endocytosis to change shape and function, processes that are orchestrated with great spatial and temporal precision.
The investigators believe that the most immediate therapeutic applications will be for diseases affecting superficial tissue such as the skin, the retina and the most external mucosal membranes.
They are now working to develop a general recipe for photoswitchable inhibitory peptides that can be used to manipulate other protein-protein interactions inside cells by applying light.
The work appeared in Angewandte Chemie (doi: 10.1002/anie.201303324).
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