Next Generation Opto‐Jasplakinolides Enable Local Remodeling of Actin Networks

• Published in: Angewandte Chemie International Edition Vol. 61; no. 48; pp. e202210220 - n/a
• Main Authors: Küllmer, Florian, Vepřek, Nynke A., Borowiak, Malgorzata, Nasufović, Veselin, Barutzki, Sebastian, Thorn‐Seshold, Oliver, Arndt, Hans‐Dieter, Trauner, Dirk
• Format: Journal Article
• Language: English
• Published: WEINHEIM Wiley 25.11.2022; Wiley Subscription Services, Inc
• Edition: International ed. in English
• Subjects: Actin; Actin Cytoskeleton; Actins; Azo compounds; Azobenzenes; Cell migration; Cell Movement; Cell proliferation; Chemistry; Chemistry, Multidisciplinary; Cytoskeleton; Depsipeptides - pharmacology; Irradiation; Jasplakinolide; Lead compounds; Natural products; Optical Control; Photopharmacology; Physical Sciences; Radiation; Science & Technology; Thermal relaxation; Wavelengths; Photopharmacology; Optical Control; NATURAL-PRODUCTS; POLYMERIZATION; MECHANISMS; LATRUNCULIN; Actin; STRUCTURAL BASIS; PROTRUSION; DYNAMICS; Cytoskeleton; Azobenzenes; AZOBENZENE PHOTOSWITCHES; BINDING
• ISSN: 1433-7851; 1521-3773; 1521-3773
• DOI: 10.1002/anie.202210220

The natural product jasplakinolide is widely used to stabilize F‐actin. Based on extensive structure–activity relationship studies, we have developed a new generation of photoswitchable jasplakinolides that feature rationally designed red‐shifted azobenzene photoswitches. Our lead compound, nOJ, can be activated with longer wavelengths in the visible range (e.g. 440–475 nm) and rapidly returns to its inactive state through thermal relaxation. nOJ enables the reversible control of F‐actin dynamics, as shown through live‐cell imaging, cell migration, and cell proliferation assays. Short, local irradiation with blue light resulted in highly localized and reversible actin aggregation with subcellular precision. Our optical tool can be useful in diverse fields to study actin dynamics with excellent spatiotemporal resolution. The study of actin dynamics in biology requires tools that can be controlled with high spatial and temporal resolution. A new photoresponsive and fast‐relaxing jasplakinolide (neo‐optojasp) allows for the stabilization of F‐actin upon irradiation with blue‐green light and provides excellent spatiotemporal control. neo‐Optojasp can be useful for studying actin dynamics with unprecedented spatiotemporal precision.