Detail
Článek
Článek online
FT
Medvik - BMČ
  • Je něco špatně v tomto záznamu ?

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

Jazyk angličtina Země Švýcarsko

Typ dokumentu časopisecké články

Perzistentní odkaz   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.

Citace poskytuje Crossref.org

000      
00000naa a2200000 a 4500
001      
bmc24019440
003      
CZ-PrNML
005      
20241024110721.0
007      
ta
008      
241015s2024 sz f 000 0|eng||
009      
AR
024    7_
$a 10.3390/ijms25158430 $2 doi
035    __
$a (PubMed)39125999
040    __
$a ABA008 $b cze $d ABA008 $e AACR2
041    0_
$a eng
044    __
$a sz
100    1_
$a Wimmer, Bjoern $u Department of Biosciences and Medical Biology, University of Salzburg, 5020 Salzburg, Austria
245    10
$a 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 / $c 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. Rakers, D. Kuhn, J. von Hagen, N. Müller, A. Rathner, H. Breitenbach-Koller
520    9_
$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.
650    12
$a tropoelastin $x metabolismus $x genetika $7 D014333
650    _2
$a lidé $7 D006801
650    12
$a ribozomální proteiny $x metabolismus $x genetika $7 D012269
650    12
$a elastin $x metabolismus $x genetika $7 D004549
650    12
$a ribozomy $x metabolismus $x účinky léků $7 D012270
650    _2
$a ligandy $7 D008024
650    _2
$a knihovny malých molekul $x farmakologie $7 D054852
655    _2
$a časopisecké články $7 D016428
700    1_
$a Schernthaner, Jan $u Department of Biosciences and Medical Biology, University of Salzburg, 5020 Salzburg, Austria
700    1_
$a Edobor, Genevieve $u Department of Biosciences and Medical Biology, University of Salzburg, 5020 Salzburg, Austria
700    1_
$a Friedrich, Andreas $u Department of Biosciences and Medical Biology, University of Salzburg, 5020 Salzburg, Austria
700    1_
$a Poeltner, Katharina $u Department of Biosciences and Medical Biology, University of Salzburg, 5020 Salzburg, Austria $1 https://orcid.org/0000000233795888
700    1_
$a Temaj, Gazmend $u Human Genetics, Faculty of Pharmacy, College UBT, 10000 Pristina, Kosovo $1 https://orcid.org/0000000348072938
700    1_
$a Wimmer, Marlies $u Department of Biosciences and Medical Biology, University of Salzburg, 5020 Salzburg, Austria
700    1_
$a Kronsteiner, Elli $u Department of Biosciences and Medical Biology, University of Salzburg, 5020 Salzburg, Austria
700    1_
$a Pichler, Mara $u Department of Biosciences and Medical Biology, University of Salzburg, 5020 Salzburg, Austria $1 https://orcid.org/000900022645998X
700    1_
$a Gercke, Hanna $u Department of Biosciences and Medical Biology, University of Salzburg, 5020 Salzburg, Austria
700    1_
$a Huber, Ronald $u Department of Biosciences and Medical Biology, University of Salzburg, 5020 Salzburg, Austria
700    1_
$a Kaefer, Niklas $u Department of Biosciences and Medical Biology, University of Salzburg, 5020 Salzburg, Austria
700    1_
$a Rinnerthaler, Mark $u Department of Biosciences and Medical Biology, University of Salzburg, 5020 Salzburg, Austria $1 https://orcid.org/0000000311900584
700    1_
$a Karl, Thomas $u Department of Biosciences and Medical Biology, University of Salzburg, 5020 Salzburg, Austria
700    1_
$a Krauß, Jan $u Department of Biosciences and Medical Biology, University of Salzburg, 5020 Salzburg, Austria
700    1_
$a Mohr, Thomas $u Department of Analytical Chemistry, Faculty of Chemistry, University of Vienna, 1090 Vienna, Austria
700    1_
$a Gerner, Christopher $u Department of Analytical Chemistry, Faculty of Chemistry, University of Vienna, 1090 Vienna, Austria $u Join Metabolome Facility, University of Vienna, Waehringer Str. 38, 1090 Vienna, Austria $1 https://orcid.org/0000000349640642
700    1_
$a Hintner, Helmut $u Department of Dermatology and Allergology, University Hospital Salzburg, Muellner Hauptstraße 48, 5020 Salzburg, Austria
700    1_
$a Breitenbach, Michael $u Department of Biosciences and Medical Biology, University of Salzburg, 5020 Salzburg, Austria $1 https://orcid.org/0000000308689036
700    1_
$a Bauer, Johann W $u Department of Dermatology and Allergology, University Hospital Salzburg, Muellner Hauptstraße 48, 5020 Salzburg, Austria
700    1_
$a Rakers, Christin $u Merck KGaA, Discovery & Development Technologies, Frankfurter Staße 250, 64293 Darmstadt, Germany
700    1_
$a Kuhn, Daniel $u Merck KGaA, Discovery & Development Technologies, Frankfurter Staße 250, 64293 Darmstadt, Germany $1 https://orcid.org/0000000205504174
700    1_
$a von Hagen, Joerg $u Merck KGaA Healthcare, Frankfurter Straße 250, 64293 Darmstadt, Germany $u ryon-Greentech Accelerator, Mainzer Straße 41, 64579 Gernsheim, Germany $1 https://orcid.org/0000000198103590
700    1_
$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
700    1_
$a Rathner, Adriana $u Institute of Biochemistry, Johannes Kepler University, Altenbergerstraße 69, 4040 Linz, Austria
700    1_
$a Breitenbach-Koller, Hannelore $u Department of Biosciences and Medical Biology, University of Salzburg, 5020 Salzburg, Austria
773    0_
$w MED00176142 $t International journal of molecular sciences $x 1422-0067 $g Roč. 25, č. 15 (2024)
856    41
$u https://pubmed.ncbi.nlm.nih.gov/39125999 $y Pubmed
910    __
$a ABA008 $b sig $c sign $y - $z 0
990    __
$a 20241015 $b ABA008
991    __
$a 20241024110715 $b ABA008
999    __
$a ok $b bmc $g 2201964 $s 1231413
BAS    __
$a 3
BAS    __
$a PreBMC-MEDLINE
BMC    __
$a 2024 $b 25 $c 15 $e 20240801 $i 1422-0067 $m International journal of molecular sciences $n Int J Mol Sci $x MED00176142
LZP    __
$a Pubmed-20241015

Najít záznam

Citační ukazatele

Možnosti archivace