New thesis provides insight into peptide aggregation

Peptide-based drugs have been central in the treatment of diabetes and cancer, among other conditions, since the early 20th century. Their high precision toward particular – including hard-to-access – targets in the body enable greater efficacy and reduced risk of side effects. At the same time, peptides present science with challenges, not least their tendency to aggregate into clusters that affect their functionality. The need for increased knowledge of the mechanisms regulating this process is significant, and in a new thesis at Uppsala University, Ellen Brunzell presents important observations.

“We have analysed how three therapeutic peptides with different properties self-assemble in solution. We have also studied how factors such as salt concentration, pH and excipients influence these processes. Using advanced scattering techniques, we can establish that even small differences in molecular structure cause large differences in self-aggregation – a conclusion that suggests the lack of universal answers as to how peptides will aggregate,” says Ellen Brunzell, PhD student at SweDeliver and the Department of Medicinal Chemistry.

In her PhD project, Brunzell has also investigated how aggregates remain stable over time, which is important in drug formulation, where peptide aggregation can be strategically used to achieve long-acting concentrations. Her thesis also demonstrates how structural analyses enable both the identification of aggregates and a deeper understanding of the mechanisms that govern their formation and stability – knowledge of great value in the development of peptide-based drugs.

“Our basic research generates results that can be applied from the laboratory to the finished drug. In addition, they provide new insights into the mechanisms underlying Alzheimer's disease and other neurodegenerative conditions. Our work is already attracting broad interest, thanks in part to close collaboration with AstraZeneca, which added industrial perspectives to our theoretical academic approach.”

Ellen Brunzell was recruited in autumn 2020 to SweDeliver and Uppsala University’s research group in Pharmaceutical Physical Chemistry. As a PhD student at the international competence centre, Brunzell has contributed to the development of the team’s research in parenteral drug delivery, now ranked at the threshold of world-leading research, with potential to take the next step. Ellen also notes she has gained many valuable skills beyond the purely pharmaceutical.

“As a PhD student at SweDeliver, you stay up to date with the latest advances in parenteral, oral and aerosol drug delivery, while receiving relevant input on your own work. Equally important are the many opportunities to practise presentation skills and the extensive networks that open up. I have benefited greatly from having a mentor from industry, Anna Franzén at Emplicure, whose experience has been invaluable and helped prepare me to pursue a career outside academia after completing my PhD.”

Text: Magnus Alsne, photo: Mikael Wallerstedt a o