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CATEGORIES:Synthetic Chemistry Research Interest Group
SUMMARY:Discovery of cyclotides and their applications in 
 peptide-based drug design - Professor David Craik 
 (Institute for Molecular Bioscience\, The Universi
 ty of Queensland)
DTSTART;TZID=Europe/London:20230227T160000
DTEND;TZID=Europe/London:20230227T170000
UID:TALK194848AThttp://talks.cam.ac.uk
URL:http://talks.cam.ac.uk/talk/index/194848
DESCRIPTION:Our work focuses on the discovery of cyclic peptid
 es in plants and their applications in drug design
  and agriculture. We have a particular interest in
  a family of proteins called cyclotides\, which co
 mprise ~30 amino acids and incorporate three disul
 fide bonds arranged in a cystine knot topology\, w
 hich makes them exceptionally stable.1 Cyclotides 
 occur in all plants from the Violaceae family and 
 in certain plants from the Rubiaceae\, Cucurbitace
 ae\, Solanaceae and Fabaceae\, where they are pres
 ent as host defence agents against insects and nem
 atodes.2 A single plant may contain dozens to hund
 reds of cyclotides expressed in a wide range of ti
 ssues\, including leaf\, flower\, stem and roots. 
 Their stability and compact structure makes cyclot
 ides an attractive protein framework onto which bi
 oactive peptide epitopes can be grafted to stabili
 se them.3 Because plants produce cyclotides in lar
 ge quantities (up to 2g/kg plant weight) we are us
 ing crop plants as expression systems for the prod
 uction of pharmaceutically active cyclotides. This
  presentation will give an overview on the discove
 ry\, biosynthesis and applications of cyclotides a
 nd also describe the use of transgenic plants as v
 ehicles for the production of cyclotide-based drug
  leads for cancer\, cardiovascular disease and pai
 n.4\n\n1.   Craik D J: Seamless proteins tie up th
 eir loose ends. Science\, 311\, 1563-1564 (2006).\
 n2.   Gilding E K\, Jackson M A\, Poth A G\, Henri
 ques S T\, Prentis P J\, Mahatmanto T\, Craik D J:
  Gene coevolution and regulation lock cyclic plant
  defence peptides to their targets. New Phytologis
 t (2016) 210\, 717-730.\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\, Ch
 an L Y\, Durek T\, Anderson M A\, Craik D J: Molec
 ular basis for the production of cyclic peptides b
 y plant asparaginyl endopeptidases. Nature Communi
 cations (2018) 9\, 2411.\n
LOCATION:Dept. of Chemistry\, Wolfson Lecture Theatre
CONTACT:Jasmine Mitchell
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