Molecular photoswitches are a class of chemical structures that can readily isomerize between distinct geometries upon irradiation with light. Molecular photoswitches are utilized to control protein structure and function with temporal and spatial precision. In this review, we summarize the recent progress in the development of azobenzene-based molecular photoswitches and their applications in the photocontrol of protein structure and function. For clarity of discussion, we divide the known photoswitchable proteins into different categories: protein motifs, ion channels, receptors, and enzymes. Basic approaches and considerations for the structure-guided design of photoswitchable ligands are discussed. The applications and limitations of current photoswitches are also discussed.
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http://dx.doi.org/10.1039/c8ob02157k | DOI Listing |
Chem Asian J
January 2025
Keio University Faculty of Science and Technology Graduate School of Science and Technology: Keio Gijuku Daigaku Rikogakubu Daigakuin Rikogaku Kenkyuka, Department of Applied Chemistry, 3-14-1 Hiyoshi, Kohoku-ku, 2238522, Yokohama, JAPAN.
For the development of new functional materials for various applications, such as drug or gene delivery and environmental remediation, the relationship between function and morphology has been considered an important aspect for controlling affinity to the targets. However, there are only a few reports on this relationship because the molecular strategy for the precise control of vesicle shape has been restricted. Herein, we report the photocontrol of vesicle shape using azobenzene-containing amphiphilic switches.
View Article and Find Full Text PDFAngew Chem Int Ed Engl
January 2025
Umeå Universitet: Umea Universitet, Department of Chemistry, Department of Chemistry, 90187, Umeå, SWEDEN.
Optogenetic systems using photosensitive proteins and chemically induced dimerization/proximity (CID/CIP) approaches enabled by chemical dimerizers (also termed molecular glues), are powerful tools to elucidate the dynamics of biological systems and to dissect complex biological regulatory networks. Here, we report a versatile chemo-optogenetic system using modular, photoswitchable molecular glues (sMGs) that can undergo repeated cycles of optical control to switch protein function on and off. We use molecular dynamics (MD) simulations to rationally design the sMGs and further expand their scope by incorporating different photoswitches, resulting in sMGs with customizable properties.
View Article and Find Full Text PDFThe mu-opioid receptor (MOR) is a major target for the treatment of pain. However, opioids are prone to side effects which limit their effectiveness as analgesics and can lead to opioid use disorders or, even, lethal overdose. The systemic administration of opioid agonists makes it both very difficult to decipher their underlying circuit mechanisms of action and to limit drug action to specific receptor subpopulations to isolate therapeutic effects from adverse side effects.
View Article and Find Full Text PDFJ Phys Chem B
January 2025
Dipartimento di Chimica, Biologia e Biotecnologie, Università di Perugia, Via Elce di Sotto, 8, 06123 Perugia, Italy.
Photoswitches are widely investigated molecules because upon exposure to selected light irradiation, they are able to undergo structural, and hence optical, changes. To fully exploit their responsiveness to irradiation, the quantum efficiency of the forward and back reactions is a fundamental parameter, whose accurate determination is critical. In this work, the spectral evolution of a biomimetic switch, which undergoes / photoinduced isomerization, is spectrophotometrically examined.
View Article and Find Full Text PDFJ Phys Chem A
December 2024
Department of Chemistry, Johns Hopkins University, 3400 N. Charles Street, Baltimore, Maryland 21218, United States.
Diaryl thieno-[3,4-]thiophenes (TT) are photoswitchable compounds that operate through reversible photoinduced cyclization/cycloreversion and have been designed specifically for integration within π-conjugated polymers to switchably manipulate polymer electronic properties. Here we report on how cross conjugating the central TT moiety impacts photocyclization dynamics as interrogated using transient absorption spectroscopy (TAS) for a series of switches built with electron-rich substituents that have various electronic interaction strengths with the TT core. For cross-conjugated structures exhibiting a propensity to switch in steady-state photoconversion experiments, ultrafast TAS reveals signatures of rapid dynamics (occurring within <1-10 ps) similar to those observed for unsubstituted switches and that are consistent with photocyclization.
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