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RiboScreenTM Technology Delivers a Ribosomal Target and a Small-Molecule Ligand for Ribosome Editing to Boost the Production Levels of Tropoelastin, the Monomeric Unit of Elastin

B. Wimmer, J. Schernthaner, G. Edobor, A. Friedrich, K. Poeltner, G. Temaj, M. Wimmer, E. Kronsteiner, M. Pichler, H. Gercke, R. Huber, N. Kaefer, M. Rinnerthaler, T. Karl, J. Krauß, T. Mohr, C. Gerner, H. Hintner, M. Breitenbach, JW. Bauer, C....

. 2024 ; 25 (15) : . [pub] 20240801

Language English Country Switzerland

Document type Journal Article

Persistent link   https://www.medvik.cz/link/bmc24019440

Elastin, a key structural protein essential for the elasticity of the skin and elastogenic tissues, degrades with age. Replenishing elastin holds promise for anti-aging cosmetics and the supplementation of elastic activities of the cardiovascular system. We employed RiboScreenTM, a technology for identifying molecules that enhance the production of specific proteins, to target the production of tropoelastin. We make use of RiboScreenTM in two crucial steps: first, to pinpoint a target ribosomal protein (TRP), which acts as a switch to increase the production of the protein of interest (POI), and second, to identify small molecules that activate this ribosomal protein switch. Using RiboScreenTM, we identified ribosomal protein L40, henceforth eL40, as a TRP switch to boost tropoelastin production. Drug discovery identified a small-molecule hit that binds to eL40. In-cell treatment demonstrated activity of the eL40 ligand and delivered increased tropoelastin production levels in a dose-dependent manner. Thus, we demonstrate that RiboScreenTM can successfully identify a small-molecule hit capable of selectively enhancing tropoelastin production. This compound has the potential to be developed for topical or systemic applications to promote skin rejuvenation and to supplement elastic functionality within the cardiovascular system.

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$a Wimmer, Bjoern $u Department of Biosciences and Medical Biology, University of Salzburg, 5020 Salzburg, Austria
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$a Elastin, a key structural protein essential for the elasticity of the skin and elastogenic tissues, degrades with age. Replenishing elastin holds promise for anti-aging cosmetics and the supplementation of elastic activities of the cardiovascular system. We employed RiboScreenTM, a technology for identifying molecules that enhance the production of specific proteins, to target the production of tropoelastin. We make use of RiboScreenTM in two crucial steps: first, to pinpoint a target ribosomal protein (TRP), which acts as a switch to increase the production of the protein of interest (POI), and second, to identify small molecules that activate this ribosomal protein switch. Using RiboScreenTM, we identified ribosomal protein L40, henceforth eL40, as a TRP switch to boost tropoelastin production. Drug discovery identified a small-molecule hit that binds to eL40. In-cell treatment demonstrated activity of the eL40 ligand and delivered increased tropoelastin production levels in a dose-dependent manner. Thus, we demonstrate that RiboScreenTM can successfully identify a small-molecule hit capable of selectively enhancing tropoelastin production. This compound has the potential to be developed for topical or systemic applications to promote skin rejuvenation and to supplement elastic functionality within the cardiovascular system.
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$a Schernthaner, Jan $u Department of Biosciences and Medical Biology, University of Salzburg, 5020 Salzburg, Austria
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$a Friedrich, Andreas $u Department of Biosciences and Medical Biology, University of Salzburg, 5020 Salzburg, Austria
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$a Poeltner, Katharina $u Department of Biosciences and Medical Biology, University of Salzburg, 5020 Salzburg, Austria $1 https://orcid.org/0000000233795888
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$a Mohr, Thomas $u Department of Analytical Chemistry, Faculty of Chemistry, University of Vienna, 1090 Vienna, Austria
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$a Hintner, Helmut $u Department of Dermatology and Allergology, University Hospital Salzburg, Muellner Hauptstraße 48, 5020 Salzburg, Austria
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$a Müller, Norbert $u Institute of Biochemistry, Johannes Kepler University, Altenbergerstraße 69, 4040 Linz, Austria $u Department of Chemistry, Faculty of Science, University of South Bohemia in Českých Budějovicích, Branišovská 1760, 370 05 České Budějovice, Czech Republic $1 https://orcid.org/0000000276213980 $7 jcu2012738279
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