Pep talk: The potential role of synthetic peptides in future antibiotics

12 Aug 2020

Prof Marc Devocelle of RCSI and SSPC. Image: Patrick Bolger

Prof Marc Devocelle of RCSI and SSPC discusses his work helping to forge synthetic peptides that could lead to future antibiotic candidates.

Prof Marc Devocelle joined the group of Prof Kevin Nolan at the Royal College of Surgeons in Ireland (RCSI) as a postdoctoral researcher and was subsequently appointed in 2000 as a manager of the institute’s newly established Peptide Synthesis Laboratory.

In 2004, he started his academic career as a lecturer in chemistry, before becoming a senior lecturer in 2008 and an associate professor of chemistry in 2014. He is currently based at RCSI and the Science Foundation Ireland Research Centre for Pharmaceuticals, SSPC, hosted by the University of Limerick.

What inspired you to become a researcher?

The possibility to work in a field that could attend to a societal need or problem, beside my passion for sciences, inspired me to become a researcher.

My first organic chemistry lecture, delivered by Prof Jacques Brocard at the University of Lille sparked a continued interest in a career in chemistry, as a researcher and a teacher.

Can you tell us about the research you’re currently working on?

My laboratory is operating as a national facility for peptide synthesis. Over the last 20 years, I had the opportunity to collaborate with several academic groups across 10 higher education institutions in Ireland on projects involving various applications and techniques of peptide chemistry.

In 2005, I started my own projects on membrane-active peptides. They focused on antimicrobial peptides (AMPs) and developing novel types of prodrugs aiming to exploit the therapeutic potential of these peptides.

More recently, my lab also developed the first peptide analogues (peptidomimetics) based on a polyethylene-glycol backbone. In 2018, I joined SSPC where my lab is working on a sustainable method for solid-phase peptide synthesis.

In your opinion, why is your research important?

Synthetic peptides are currently the fifth main origin of pipeline drugs. Their compound annual growth rate is approaching the one of small molecules already and could progress further if some issues threatening the clinical development of therapeutic peptides are addressed.

This includes solutions overcoming the limited bioavailability and/or stability of peptide leads (eg drug delivery techniques such as prodrugs, or peptidomimetic conversion), as well as the use of green alternative to solvents for peptide synthesis listed on the European Commission’s Reach Annex XVII of restricted substances (eg synthesis in aqueous medium).

What commercial applications do you foresee for your research?

They could include novel mechanism antibiotic candidates based on AMPs and a sustainable industrial process for the large-scale production of peptides to be used as therapeutics, components of biomaterials, nanomedicines, peptide conjugates etc.

What are some of the biggest challenges you face as a researcher in your field?

Progress in this field is highly contingent on successful academia-industry partnerships. These can be difficult to develop during the proof-of-concept or early phases of projects developing novel approaches.

Are there any common misconceptions about this area of research?

In the past, peptides have experienced a number of significant drawbacks as therapeutic candidates. These limitations are still commonly associated with them, despite significant progress in the field of peptide drugs – such as their synthesis, purification, modification and delivery – besides the increasing number of successful applications.

I think publications originating from the pharmaceutical industry itself can make a difference.

What are some of the areas of research you’d like to see tackled in the years ahead?

Peptides are structurally between low molecular weight compounds and antibodies. It will be interesting to see applications bridging these two classes of therapeutic entities emerging in the years ahead, such as the ability to bind to large surface areas with high affinity and specificity.

It will also be interesting to see the coalition of different peptide-based research areas at the forefront of the biological, chemical, computational and biophysical sciences alongside synthetic access to increasingly large peptides and proteins.

Are you a researcher with an interesting project to share? Let us know by emailing with the subject line ‘Science Uncovered’.