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SUMMARY:Diversity Oriented Biosynthesis: Making Complex Cyclic Peptides Us
 ing a Combination of Synthesis and Enzymes - Prof. Marcel Jaspars (Marine 
 Biodiscovery Centre\, Department of Chemistry\, University of Aberdeen)
DTSTART:20190405T100000Z
DTEND:20190405T110000Z
UID:TALK121681@talks.cam.ac.uk
CONTACT:Lingtao Kong
DESCRIPTION:Cyclic peptides are an exciting and underexplored group of com
 pounds with unique biological properties. They are preferred to linear var
 iants as they can cross cell membranes and are more stable to metabolic en
 zymes. There is currently a pressing need especially within the pharmaceut
 ical sector for testing compound libraries based on these scaffolds which 
 share with biologics the ability to modulate the challenging protein-prote
 in interactions and are much cheaper and can be orally administered. Novel
  cyclic peptides can be designed in silico that could have promising thera
 peutic properties but currently have no method of manufacture. Therefore\,
  efficient and low-cost catalytic methods to produce them are in demand.\n
 Cyanobactins are complex cyclic peptides containing heterocycles\, D-stere
 ocentres and prenylated residues produced by the action of post-translatio
 n modifying enzymes on a precursor peptide (Figure 1). We have structurall
 y defined all the main enzymes involved in their production – the hetero
 cyclase\, azoline oxidase\, protease\, macrocyclase and prenylase\, and ha
 ve generated systems to produce complex cyclic peptides using these enzyme
 s1\,2\,3. The more efficient system relies on the use of engineered enzyme
 s that can act on simplified synthetic substrates3 and generate molecules 
 containing multiple non-amino acid moieties4. This chemoenzymatic approach
  is being commercialised to generate complex cyclic peptides that can be u
 sed to treat complex diseases mediated by protein-protein interactions\, s
 uch as immune disorders.\n\nFigure 1. The enzymes involved in formation of
  the patellamides.\n1.	 “An Efficient Method for the In Vitro Production
  of Azoline-Based Cyclic Peptides.” Wael E. Houssen\, Andrew F. Bent\, A
 ndrew R. McEwan\, Nathalie Pieiller\, Jioji Tabudravu\, Jesko Koehnke\, Gr
 eg Mann\, Rosemary I. Adaba\, Louise Thomas\, Usama W. Hawas\, Huanting Li
 u\, Ulrich Schwarz-Linek\, Margaret C. M. Smith\, James H. Naismith\, Marc
 el Jaspars\, Angew. Chem.-Int. Ed. 2014 53 14171\n2.	“Structural Analysi
 s of Leader Peptide Binding Enables Leader-Free Cyanobactin Processing” 
 Jesko Koehnke\, Greg Mann\, Andrew F Bent\, Hannes Ludewig\, Sally Shirran
 \, Catherine Botting\, Tomas Lebl\, Wael E Houssen\, Marcel Jaspars\, & Ja
 mes H Naismith Nat Chem Biol 2015\, 11\, 558\n3.	“Synthesis of hybrid cy
 clopeptides through enzymatic macrocyclisation” Emilia Oueis\, Bruno Nar
 done\, Marcel Jaspars\, Nicholas J. Westwood and James H. Naismith\, Chemi
 stryOpen 2017\, 6\, 11-14\n
LOCATION:Unilever  Lecture Theatre\,  Department of Chemistry
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