WeightNameValue
1000 Titel
  • A modular toolkit to inhibit proline-rich motif–mediated protein–protein interactions
1000 Autor/in
  1. Opitz, Robert |
  2. Müller, Matthias |
  3. Reuter, Cédric |
  4. Barone, Matthias |
  5. Soicke, Arne |
  6. Roske, Yvette |
  7. Piotukh, Kirill |
  8. Huy, Peter |
  9. Beerbaum, Monika |
  10. Wiesner, Burkhard |
  11. Beyermann, Michael |
  12. Freund, Christian |
  13. Volkmer, Rudolf |
  14. Oschkinat, Hartmut |
  15. Schmalz, Hans-Günther |
  16. Kühne, Ronald |
  17. Schmieder, Peter |
1000 Erscheinungsjahr 2015
1000 LeibnizOpen
1000 Publikationstyp
  1. Artikel |
1000 Online veröffentlicht
  • 2015-04-21
1000 Erschienen in
1000 Quellenangabe
  • 112(16): 5011–5016
1000 FRL-Sammlung
1000 Verlagsversion
  • https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4413326/ |
  • http://doi.org/10.1073/pnas.1422054112 |
1000 Ergänzendes Material
  • http://www.pnas.org/lookup/suppl/doi:10.1073/pnas.1422054112/-/DCSupplemental |
1000 Publikationsstatus
1000 Begutachtungsstatus
1000 Sprache der Publikation
1000 Abstract/Summary
  • Small-molecule competitors of protein–protein interactions are urgently needed for functional analysis of large-scale genomics and proteomics data. Particularly abundant, yet so far undruggable, targets include domains specialized in recognizing proline-rich segments, including Src-homology 3 (SH3), WW, GYF, and Drosophila enabled (Ena)/vasodilator-stimulated phosphoprotein (VASP) homology 1 (EVH1) domains. Here, we present a modular strategy to obtain an extendable toolkit of chemical fragments (ProMs) designed to replace pairs of conserved prolines in recognition motifs. As proof-of-principle, we developed a small, selective, peptidomimetic inhibitor of Ena/VASP EVH1 domain interactions. Highly invasive MDA MB 231 breast-cancer cells treated with this ligand showed displacement of VASP from focal adhesions, as well as from the front of lamellipodia, and strongly reduced cell invasion. General applicability of our strategy is illustrated by the design of an ErbB4-derived ligand containing two ProM-1 fragments, targeting the yes-associated protein 1 (YAP1)-WW domain with a fivefold higher affinity.
1000 Sacherschließung
lokal protein–protein interaction
lokal cell migration
lokal actin cytoskeleton
lokal Ena
lokal VASP
1000 Fächerklassifikation (DDC)
1000 Liste der Beteiligten
  1. https://frl.publisso.de/adhoc/creator/T3BpdHosIFJvYmVydA==|https://frl.publisso.de/adhoc/creator/TcO8bGxlciwgTWF0dGhpYXM=|https://frl.publisso.de/adhoc/creator/UmV1dGVyLCBDw6lkcmlj|https://frl.publisso.de/adhoc/creator/QmFyb25lLCBNYXR0aGlhcw==|https://frl.publisso.de/adhoc/creator/U29pY2tlLCBBcm5l|https://frl.publisso.de/adhoc/creator/Um9za2UsIFl2ZXR0ZQ==|https://frl.publisso.de/adhoc/creator/UGlvdHVraCwgS2lyaWxs|https://frl.publisso.de/adhoc/creator/SHV5LCBQZXRlcg==|https://frl.publisso.de/adhoc/creator/QmVlcmJhdW0sIE1vbmlrYQ==|https://frl.publisso.de/adhoc/creator/V2llc25lciwgQnVya2hhcmQ=|https://frl.publisso.de/adhoc/creator/QmV5ZXJtYW5uLCBNaWNoYWVs|https://frl.publisso.de/adhoc/creator/RnJldW5kLCBDaHJpc3RpYW4=|https://frl.publisso.de/adhoc/creator/Vm9sa21lciwgUnVkb2xm|https://frl.publisso.de/adhoc/creator/T3NjaGtpbmF0LCBIYXJ0bXV0|https://frl.publisso.de/adhoc/creator/U2NobWFseiwgSGFucy1Hw7xudGhlcg==|https://frl.publisso.de/adhoc/creator/S8O8aG5lLCBSb25hbGQ=|http://orcid.org/0000-0001-9968-9327
1000 Label
1000 Förderer
  1. Deutsche Forschungsgemeinschaft |
1000 Fördernummer
  1. KU 845; SCHM 857; BE 1434; SFB765
1000 Förderprogramm
  1. -
1000 Förderung
  1. 1000 joinedFunding-child
    1000 Förderer Deutsche Forschungsgemeinschaft |
    1000 Förderprogramm -
    1000 Fördernummer KU 845; SCHM 857; BE 1434; SFB765
1000 Objektart article
1000 Beschrieben durch
1000 @id frl:6405497.rdf
1000 Erstellt am 2017-11-27T15:52:08.576+0100
1000 Erstellt von 25
1000 beschreibt frl:6405497
1000 Bearbeitet von 218
1000 Zuletzt bearbeitet Fri Dec 04 12:26:59 CET 2020
1000 Objekt bearb. Fri Dec 04 12:26:59 CET 2020
1000 Vgl. frl:6405497
1000 Oai Id
  1. oai:frl.publisso.de:frl:6405497 |
1000 Sichtbarkeit Metadaten public
1000 Sichtbarkeit Daten public
1000 Gegenstand von

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