SwePub
Sök i LIBRIS databas

  Extended search

WFRF:(Akcan Muharrem)
 

Search: WFRF:(Akcan Muharrem) > Oxytocic plant cycl...

  • Koehbach, Johannes (author)

Oxytocic plant cyclotides as templates for peptide G protein-coupled receptor ligand design

  • Article/chapterEnglish2013

Publisher, publication year, extent ...

  • 2013-11-18
  • Proceedings of the National Academy of Sciences,2013
  • printrdacarrier

Numbers

  • LIBRIS-ID:oai:DiVA.org:uu-215901
  • https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-215901URI
  • https://doi.org/10.1073/pnas.1311183110DOI

Supplementary language notes

  • Language:English
  • Summary in:English

Part of subdatabase

Classification

  • Subject category:ref swepub-contenttype
  • Subject category:art swepub-publicationtype

Notes

  • Cyclotides are plant peptides comprising a circular backbone and three conserved disulfide bonds that confer them with exceptional stability. They were originally discovered in Oldenlandia affinis based on their use in traditional African medicine to accelerate labor. Recently, cyclotides have been identified in numerous plant species of the coffee, violet, cucurbit, pea, potato, and grass families. Their unique structural topology, high stability, and tolerance to sequence variation make them promising templates for the development of peptide-based pharmaceuticals. However, the mechanisms underlying their biological activities remain largely unknown; specifically, a receptor for a native cyclotide has not been reported hitherto. Using bioactivity-guided fractionation of an herbal peptide extract known to indigenous healers as "kalata-kalata," the cyclotide kalata B7 was found to induce strong contractility on human uterine smooth muscle cells. Radioligand displacement and second messenger-based reporter assays confirmed the oxytocin and vasopressin V-1a receptors, members of the G protein-coupled receptor family, as molecular targets for this cyclotide. Furthermore, we show that cyclotides can serve as templates for the design of selective G protein-coupled receptor ligands by generating an oxytocin-like peptide with nanomolar affinity. This nonapeptide elicited dose-dependent contractions on human myometrium. These observations provide a proof of concept for the development of cyclotide-based peptide ligands.

Subject headings and genre

  • circular plant peptide
  • peptide ligand design
  • uterotonic
  • chemical pharmacology
  • peptide drugs

Added entries (persons, corporate bodies, meetings, titles ...)

  • O'Brien, Margaret (author)
  • Muttenthaler, Markus (author)
  • Miazzo, Marion (author)
  • Akcan, Muharrem (author)
  • Elliott, Alysha G. (author)
  • Daly, Norelle L. (author)
  • Harvey, Peta J. (author)
  • Arrowsmith, Sarah (author)
  • Gunasekera, SunithiUppsala universitet,Avdelningen för farmakognosi(Swepub:uu)sugun274 (author)
  • Smith, Terry J. (author)
  • Wray, Susan (author)
  • Göransson, UlfUppsala universitet,Avdelningen för farmakognosi(Swepub:uu)ugo29049 (author)
  • Dawson, Philip E. (author)
  • Craik, David J. (author)
  • Freissmuth, Michael (author)
  • Gruber, Christian W. (author)
  • Uppsala universitetAvdelningen för farmakognosi (creator_code:org_t)

Related titles

  • In:Proceedings of the National Academy of Sciences of the United States of America: Proceedings of the National Academy of Sciences110:52, s. 21183-211880027-84241091-6490

Internet link

Find in a library

To the university's database

Kungliga biblioteket hanterar dina personuppgifter i enlighet med EU:s dataskyddsförordning (2018), GDPR. Läs mer om hur det funkar här.
Så här hanterar KB dina uppgifter vid användning av denna tjänst.

 
pil uppåt Close

Copy and save the link in order to return to this view