2023-24-project-catalogue

###Chemical Synthesis of Sactipeptides as New Generation Antimicrobials

Project ID: 2228bd1169 (You will need this ID for your application)

Research Theme: Healthcare Technologies

UCL Lead department: School of Pharmacy

Department Website

Lead Supervisor: Rachael Dickman

Project Summary:

Background

Sactipeptides are a group of peptide natural products which are characterised by the crosslinked amino acid sactionine. Although they have excellent antimicrobial activity, most sactipeptides have poor physical properties. Currently, medicinal chemistry efforts towards improving these properties are prevented by a lack of methods to chemically synthesise sactionines or sactipeptides. This limits their therapeutic potential.

The aim of this work is to address this issue by developing a robust method for the synthesis of sactionine residues, and use this to chemically synthesise a sactipeptide for the first time.

What you will be doing

The proposed approach for this project involves synthesising the sactionine bridge as a protected amino acid. This allows complete control of the location and stereochemistry of the crosslink in the peptide. Several different routes will be explored towards sactionine synthesis, including exploring batch and flow chemistry strategies. Once an optimum sactionine synthesis has been identified, its suitability will be demonstrated by the synthesis of a natural sactipeptide.

Why this research is important

The rapid rise of antimicrobial resistance means that new antibiotics are urgently needed. Natural products have historically been a rich source of antimicrobials. With the development of the new synthetic methods in this project, the potential of sactipeptides as new generation antibiotics can be realised.

Who you will be working with

The Dickman group is a multidisciplinary team of chemists and biologists focussing on development of therapeutic peptides. This project will contribute a new synthetic dimension to our growing sactipeptide research programme.

Who we are looking for

We are looking for someone with a background in chemistry or pharmacy. Laboratory experience in synthetic organic chemistry would be advantageous. Required training will be provided as necessary in: synthetic chemistry (batch and flow), solid-phase peptide synthesis, compound characterisation (including NMR and mass spectrometry), HPLC.