HIPS Talk “Modifying peptides: Combining chemistry and biology“
Various peptide macrocycles originating from natural products have been known for a long time to be effective medicines for a number of conditions. More recently these molecules have attracted considerable interest as potential therapeutic starting points particularly in disrupting protein protein interfaces.
Our lab has focussed on the enzymes involved in patellamide biosynthesis following the ground breaking work of Schmidt in mapping out the gene cluster. Patellamides are the exemplar of the cyanobactin class of macrocyclic peptides and contain multiple chemical modifications. We have characterised all the enzymes in the pathway at both structural and mechanistic level. We have used this information to engineer the enzymes to be useful for in vitro synthesis. We have been able to make peptide non-peptide hybrid macrocycles and a small library of macrocycles which we tested for biological activity.
I will report our progress on combining solid phase synthetic chemistry to generate libraries coupled to enzymes. I will discuss very recent work on new classes of modifying enzymes that are not in the patellamide pathway but have significant potential.
There is opportunity to talk with the speaker before the talk.
Building and room
Blg E8.1, Seminar Room (Ground Floor)
Prof. James H. Naismith
Structural Biology, University of Oxford
Jim Naismith trained as a chemist at Edinburgh graduating 1989. He then completed a PhD in structural biology at Manchester as a Carnegie Scholar. As a NATO fellow he worked at the University of Texas Southwester Medical Centre Dallas. He returned to the UK in 1995 where his lab at St Andrews worked at the interface of chemistry and biology. He directed the University of St Andrews’s flagship research institute the Biomedical Science Research Complex, a joint effort of Medicine, Biology, Chemistry and Physics. He moved to Oxford in 2017 and is the head of the Research Complex at Harwell. His lab works in structural biology of natural product biosynthesis and in the transport of complex carbohydrates in gram negative bacteria.
Dr. Jesko Köhnke