uu.seUppsala universitets publikationer
Ändra sökning
RefereraExporteraLänk till posten
Permanent länk

Direktlänk
Referera
Referensformat
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Annat format
Fler format
Språk
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Annat språk
Fler språk
Utmatningsformat
  • html
  • text
  • asciidoc
  • rtf
Chemical Proteomics for Target Discovery of Head-to-Tail Cyclized Mini-Proteins
Med Univ Vienna, Ctr Physiol & Fharmacol, Vienna, Austria.;Univ Nat Resources & Life Sci BOKU, Dept Agobiotechnol, Ctr Analyt Chem, Vienna, Austria..
Med Univ Vienna, Ctr Physiol & Fharmacol, Vienna, Austria..
Med Univ Vienna, Ctr Physiol & Fharmacol, Vienna, Austria..
Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Avdelningen för farmakognosi.
Visa övriga samt affilieringar
2017 (Engelska)Ingår i: Frontiers in Chemistry, E-ISSN 2296-2646, Vol. 5, artikel-id 73Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

Target deconvolution is one of the most challenging tasks in drug discovery, but a key step in drug development. In contrast to small molecules, there is a lack of validated and robust methodologies for target elucidation of peptides. In particular, it is difficult to apply these methods to cyclic and cysteine-stabilized peptides since they exhibit reduced amenability to chemical modification and affinity capture; however, such ribosomally synthesized and post-translationally modified peptide natural products are rich sources of promising drug candidates. For example, plant-derived circular peptides called cyclotides have recently attracted much attention due to their immunosuppressive effects and oral activity in the treatment of multiple sclerosis in mice, but their molecular target has hitherto not been reported. In this study, a chemical proteomics approach using photo-affinity crosslinking was developed to determine a target for the circular peptide [T20K]kalata B1. Using this prototypic nature-derived peptide enabled the identification of a possible functional modulation of 14-3-3 proteins. This biochemical interaction was validated via competition pull down assays as well as a cellular reporter assay indicating an effect on 14-3-3-dependent transcriptional activity. As proof of concept, the presented approach may be applicable for target elucidation of various cyclic peptides and mini-proteins, in particular cyclotides, which represent a promising class of molecules in drug discovery and development.

Ort, förlag, år, upplaga, sidor
FRONTIERS MEDIA SA , 2017. Vol. 5, artikel-id 73
Nyckelord [en]
cyclotides, cyclic protein, chemical proteomics, peptide-protein interaction, photo-affinity labeling
Nationell ämneskategori
Farmaceutiska vetenskaper
Identifikatorer
URN: urn:nbn:se:uu:diva-338516DOI: 10.3389/fchem.2017.00073ISI: 000412726000001PubMedID: 29075625OAI: oai:DiVA.org:uu-338516DiVA, id: diva2:1173892
Forskningsfinansiär
Australian Research Council, FT140100730Tillgänglig från: 2018-01-15 Skapad: 2018-01-15 Senast uppdaterad: 2018-01-15Bibliografiskt granskad

Open Access i DiVA

fulltext(2107 kB)79 nedladdningar
Filinformation
Filnamn FULLTEXT01.pdfFilstorlek 2107 kBChecksumma SHA-512
4550f72cf5d48e5ce05e6a3c75ebf941dd8b61184fdadc29fe3150069b24eef78c893d8b669cfde7ee1b2e899c551ab0244f5e762777b244f04a48da4b91342d
Typ fulltextMimetyp application/pdf

Övriga länkar

Förlagets fulltextPubMed

Personposter BETA

Muhammad, TajGunasekera, SunithiGöransson, Ulf

Sök vidare i DiVA

Av författaren/redaktören
Muhammad, TajGunasekera, SunithiGöransson, Ulf
Av organisationen
Avdelningen för farmakognosi
I samma tidskrift
Frontiers in Chemistry
Farmaceutiska vetenskaper

Sök vidare utanför DiVA

GoogleGoogle Scholar
Totalt: 79 nedladdningar
Antalet nedladdningar är summan av nedladdningar för alla fulltexter. Det kan inkludera t.ex tidigare versioner som nu inte längre är tillgängliga.

doi
pubmed
urn-nbn

Altmetricpoäng

doi
pubmed
urn-nbn
Totalt: 99 träffar
RefereraExporteraLänk till posten
Permanent länk

Direktlänk
Referera
Referensformat
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Annat format
Fler format
Språk
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Annat språk
Fler språk
Utmatningsformat
  • html
  • text
  • asciidoc
  • rtf