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SUMMARY:Discovery of cyclotides and their applications in peptide-based dr
 ug design - Professor David Craik (Institute for Molecular Bioscience\, Th
 e University of Queensland)
DTSTART:20230227T160000Z
DTEND:20230227T170000Z
UID:TALK194869@talks.cam.ac.uk
CONTACT:111982
DESCRIPTION:Our work focuses on the discovery of cyclic peptides in plants
  and their applications in drug design and agriculture. We have a particul
 ar interest in a family of proteins called cyclotides\, which comprise ~30
  amino acids and incorporate three disulfide bonds arranged in a cystine k
 not topology\, which makes them exceptionally stable.1 Cyclotides occur in
  all plants from the Violaceae family and in certain plants from the Rubia
 ceae\, Cucurbitaceae\, Solanaceae and Fabaceae\, where they are present as
  host defence agents against insects and nematodes.2 A single plant may co
 ntain dozens to hundreds of cyclotides expressed in a wide range of tissue
 s\, including leaf\, flower\, stem and roots. Their stability and compact 
 structure makes cyclotides an attractive protein framework onto which bioa
 ctive peptide epitopes can be grafted to stabilise them.3 Because plants p
 roduce cyclotides in large quantities (up to 2g/kg plant weight) we are us
 ing crop plants as expression systems for the production of pharmaceutical
 ly active cyclotides. This presentation will give an overview on the disco
 very\, biosynthesis and applications of cyclotides and also describe the u
 se of transgenic plants as vehicles for the production of cyclotide-based 
 drug leads for cancer\, cardiovascular disease and pain.4\n\n1.   Craik D 
 J: Seamless proteins tie up their loose ends. Science\, 311\, 1563-1564 (2
 006).\n2.   Gilding E K\, Jackson M A\, Poth A G\, Henriques S T\, Prentis
  P J\, Mahatmanto T\, Craik D J: Gene coevolution and regulation lock cycl
 ic plant defence peptides to their targets. New Phytologist (2016) 210\, 7
 17-730.\n3.   Wang C K\, Craik D J: A designer’s guide to the making of 
 macrocycles. Nature Chemical Biology (2018) 14\, 417-427.\n4.   Jackson M 
 A\, Gilding E K\, Shafee T\, Harris K\, Kaas Q\, Poon S\, Yap K\, Jia H\, 
 Guarino R\, Chan L Y\, Durek T\, Anderson M A\, Craik D J: Molecular basis
  for the production of cyclic peptides by plant asparaginyl endopeptidases
 . Nature Communications (2018) 9\, 2411.
LOCATION:Department of Chemistry\, Cambridge\, Wolfson Lecture Theatre
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