Photopharmacology and Photochemical Biology (2021)

The use of light as treatment dates back to ancient civilizations. However, it was the discovery of green fluorescent protein that led to a paradigm shift in our ability to observe and study cellular processes. Applying light to the investigation of the spatial and temporal dynamics of protein location, structure, and function has enabled biological discoveries that were previously unimaginable and has made significant contributions to both the understanding and treatment of human diseases. Now, researchers are going beyond using optical probes for visualization by introducing powerful approaches for perturbation and manipulation of cellular function. Using light as an external trigger enables the control of biological processes with the same level of spatio-temporal resolution present in nature. In addition to this, light is an ideal tool since it is bioorthogonal and minimally invasive – if applied correctly. Furthermore, the wavelength, intensity, and duration of irradiation can be precisely tuned, enabling not only rapid, full activation but also finely graded changes in biological responses. Importantly, in a single system, different wavelengths can be used for the activation or deactivation of different processes providing independent control. These opportunities, which were already recognized decades ago, for example in the synthesis of caged ATP and in the development of photodynamic therapy, are now combined with innovations in fluorophore chemistry, drug design, and device engineering, leading to the recent bloom of this inherently interdisciplinary field. In this regard, new research areas such as optogenetics and photopharmacology have emerged. This Special Collection in ChemPhotoChem contains publications that present novel light-responsive compounds, for example enzyme inhibitors, oligonucleotides, photosensitizers, and small organic molecules, which can be selectively activated, uncaged, or photoswitched. Furthermore, this collection describes efforts to bring forward in vivo application of such systems, for example by improving pharmacokinetic properties and by developing innovative methodologies capable of activation in living organisms. In addition to important discovery-based research, many of these studies are focused on translational goals, to ultimately provide innovative treatments that address unmet clinical needs. The chemistry–biology interface is uniquely suited to advance the optical control of biological processes by combining the engineering and new discovery of chromophores with the manipulation and study of pharmacological agents and biological macromolecules. We hope that this Special Collection will inspire experts in the field and prompt researchers from other disciplines to join us in the application of light to investigate open questions in biology and human health. Finally, we would like to express our gratitude to all the authors who have contributed to this collection, and we look forward to seeing the newest developments in photopharmacology and optochemical biology in the coming years. A.D. acknowledges support from the National Institutes of Health (R01 GM127153 and R01 GM132565) and the National Science Foundation (CHE-1904972). O.V. acknowledges support from the Deutsche Forschungsgemeinschaft (DFG) for: TRR81 “Chromatin Changes in Differentiation and Malignancies” (project TRR81/3 Z04; SPP1926 “Next Generation Optogenetics” (project VA 1002/4-1; AOBJ 65927); and project VA 1002/5-1; AOBJ: 666911. Alexander Deiters received his PhD from the University of Münster (Germany) in 2000 and subsequently did postdoctoral studies at the University of Texas and The Scripps Institute (USA). He currently is a professor at the University of Pittsburgh, where his group conducts research at the interface of chemistry and biology, with an emphasis on small-molecule and optical control of oligonucleotide and protein function in cells and animals. Susanne Kossatz is an Assistant Professor in the Department of Nuclear Medicine and the Central Institute for Translational Cancer Research (TranslaTUM) at Technical University Munich. She obtained a PhD in Molecular Imaging from the Friedrich Schiller University in Jena (Germany) and conducted her postdoctoral studies at Memorial Sloan Kettering Cancer Center in New York City, NY (USA), before assuming her current position in Munich. Her research interests involve the development and clinical translation of molecular imaging tools for improved tumor detection, intraoperative delineation, treatment and monitoring with the long-term goal to improve outcome and survival for patients. Her research is focused on the design and investigation of fluorescent and nuclear imaging probes for their suitability in molecular imaging applications, their preclinical validation and clinical translation. Olalla Vázquez received her PhD in Organic Chemistry (2010) from the University of Santiago de Compostela (Spain) under the supervision of Prof. Jose Luis Mascareñas and Prof. Eugenio M. Vázquez, with visits during her studies to the labs of Prof. Gregory L. Verdine (2006) at Harvard University and Prof. Oliver Seitz (2008) at Humboldt Universität zu Berlin. Afterwards, she returned to Berlin as a Marie Curie postdoctoral fellow. In 2014 she was appointed Assistant Professor (W1) at the University of Marburg to manage the newborn Chemical Biology division. In April 2020, Olalla successfully passed her tenure evaluation and was promoted to Associate Professor (W2) in January 2021. Her main interests are focused on the development of innovative optochemical tools combining organic chemistry and biological approaches.