Peptide and Protein Chemistry Group

Our aim is to refine peptide synthesis to make even more complex and challenging peptides and develop new therapeutic agents. Our targets include insulin-like peptides and antimicrobial peptides, which both have important roles in treatment of diabetes and infections.

Research interests

  • Peptide and protein chemistry
  • Peptide drug design and development
  • Chemical and enzyme-based peptide synthesis
  • Sustainable peptide chemistry
  • Antimicrobial peptides
Techniques

  • Chemical peptide synthesis
  • Enzyme-mediated peptide synthesis
  • Novel peptide biomaterials manufacture
  • In vitro cellular assays

About our research

Because of their high specificity and low toxicity profiles, peptides are increasingly sought-after alternatives to small molecule therapeutics, and a major focus for the biotech and pharmaceutical industry for creating next-generation products. Today, the peptide market is growing nearly twice as fast as the overall pharmaceutical market due to an increased number of therapeutic targets and improved delivery methodologies. There are now 70 therapeutic peptides on the market, 200 in clinical phases, and 600 in advanced pre-clinical stages.

The industrial manufacture of large peptides and proteins in high quality and cost-effectively is generally via recombinant DNA means. However, this is restricted to native or near-native forms of endogenous proteins only. Only chemical methods can produce peptide modifications (i.e. peptidomimetics) for engineering greater potency and longer in vivo half-lives or to site-selectively add functional moieties such as a sugars or lipids.

Solid phase peptide synthesis (SPPS) is the key chemical technology to produce such peptides but has practical and cost limitations with respect to the size and scalability. A recent development, native chemical ligation (NCL), allows synthesis of proteins by simple solution ligation of two (or more) shorter synthetic peptide segments in a controlled manner.

Our team’s projects focus on the preparation and chemical and biological study of peptides with a focus on those that play a role in glucose regulation (insulin-like peptides, incretins such as exenatide) and in combatting infections (antimicrobial peptides). We use modern synthetic methods to produce these complex biomolecules and to subject them to subsequent bioassays and screening for improved functional activity.

Research team

Research team head

Professor John Wade

Group Head

Team members

Research and technical staff

  • Feng Lin

Selected publications

  • Li W, Lin F, Hung AJ, Barlow AJ, Sani M-A, Paolini R, Singleton WGB, Holden JE, Hossain MA, Separovic F, O’Brien-Simpson NM and Wade JD (2022), ‘Enhancing proline-rich antimicrobial peptide action by homodimerization: influence of bifunctional linker’, Chemical Science, 13(8):2226–2237, doi:10.1039/d1sc05662j
  • Li W, Separovic F, O’Brien-Simpson NM and Wade JD (2021), ‘Chemically modified and conjugated antimicrobial peptides against superbugs’, Chemical Society Reviews, 50(8):4932–4973, doi:10.1039/D0CS01026J
  • Hossain MA and Wade JD (2017), ‘Novel methods for the chemical synthesis of insulin superfamily peptides and of analogues containing disulfide isosteres, Accounts of Chemical Research, 50(9):2116–2127, doi:10.1021/acs.accounts.7b00288

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