Could A Small Flower Hold The Key to More Stable Peptide Drugs?

By Megan Craig, M.Sc.Nov 29 2023

Taking inspiration from a small purple flower found in the tropics, University of Bath scientists have successfully created a new tool that could help to create more stable, efficient and cost-effective drugs.

The new development addresses the pharmaceutical industry's shift towards peptide-based medications, offering a cleaner, greener, and more economical alternative for drug development. This advancement holds promise not only in pharmaceuticals but also in other industries like biotechnology, food, and bioenergy, where peptide stability and functionality are crucial.

Harnessing Nature's Design for Drug Development

The research, published in the Journal of the American Chemical Society Gold (JACS Au), focuses on improving the stability and delivery of peptide-based drugs.

Traditional small molecules, while effective, often fall short in blocking protein interactions—a key mechanism in disease treatment. Consequently, the industry is turning to small proteins or 'peptides'. However, these peptides face challenges: they can unravel, are sensitive to temperature, and struggle to penetrate cells.

The team's solution involves creating "cyclic" proteins and peptides by connecting their start and end points. This approach significantly enhances their heat and chemical stability and eases cell entry.

While the method draws from a typically slow and low yielding naturally occuring process in plants, the Bath team has created a method leveraging an enzyme from the Oldenlandia affinis plant, modified and transferred into bacterial cells for mass production. This system dramatically improves yield, uses environmentally friendly reagents, and simplifies the production process.

Innovative Cyclic Protein Production

Professor Jody Mason, a key figure in the project, notes the robustness conferred by cyclisation, a process that the Oldenlandia plant uses for defense. By combining this natural mechanism with bacterial protein-producing technology, the team developed a powerful tool that has significant implications for drug discovery.

Dr. Simon Tang, Research Associate, emphasizes the potential of this technique in overcoming the cost and complexity barriers in producing therapeutic peptides and proteins. The process not only simplifies production but also reduces environmental impact, offering a cleaner approach to drug manufacturing.

We’re really excited about the potential applications of this, not only for the pharmaceutical industry but other industries such as the food industry, detergent industry, in biotechnology, and in bioenergy production.

Dr. Simon Tang, Research Associate, University of Bath’s Department of Life Sciences

To showcase the technology's potential, the researchers applied their method to a protein called DHFR. The cyclic version of DHFR displayed increased resistance to temperature changes while maintaining its normal function. This demonstrates the process's ability to enhance protein stability without compromising efficacy, a key consideration in drug development.

The research involved advanced molecular cloning techniques and recombinant expression in E. coli. The cyclic proteins were produced by co-expressing the modified OaAEP1 enzyme with the target protein, mDHFR, in this case. The process was confirmed using various analytical techniques, including mass spectrometry and circular dichroism. Generally, this methodology simplifies the production of cyclic peptides and has broad applications in biochemical and chemical industries.

Conclusion and Future Prospects

This development represents a significant step forward in peptide-based drug development. With a patent filed, the researchers have opened new avenues for the production of stable, efficient, and environmentally friendly drugs. The technique's simplicity, cost-effectiveness, and green approach hold promise for widespread adoption across multiple industries, with great potential for the landscape of drug manufacturing and beyond.