A groundbreaking study published by a team of researchers from the École Polytechnique Fédérale de Lausanne (EPFL) has vast implications for the future of peptide drug development and research. The team, led by scientists including Mischa Schüttel, Edward Will, Gontran Sangouard, Anne Zarda, Sevan Habeshian, and Alexander L. Nielsen, has modified a commercially available peptide synthesizer to accommodate 384-well plates, four times the capacity of the current standard. This advancement enables the synthesis of 1,536 peptides in a single run, offering unprecedented efficiency in peptide production. Published in the “Journal of Peptide Science”, this research, supported by the Swiss National Science Foundation, represents a significant leap forward in the field of combinatorial chemistry and epitope mapping.
Solid-Phase Peptide Synthesis (SPPS): A Quantum Leap in Efficiency
Solid-phase peptide synthesis (SPPS) has evolved significantly since its introduction by Robert Bruce Merrifield in 1963. This novel approach, for which Merrifield won a Nobel Prize, revolutionized the way chemists create peptides. The latest advancements reported by the EPFL team underscore a pivotal shift from the 96-well microplate reactors to a more robust 384-well format. With this newly developed technology, high throughput is no longer a hurdle for laboratories aiming to synthesize large peptide libraries rapidly.
The Age of Direct Bioactivity Screening
This leap in peptide synthesis directly benefits bioactivity screening. The produced peptides exhibit an average purity greater than 80%, with concentrations exceeding 10 mM, and quantities averaging more than 0.5 μmol, negating the need for prior chromatographic purification. This means that scientists can rapidly test thousands of peptide sequences to identify those with potential therapeutic effects or diagnostic value with far less time and resource expenditure.
Potential Applications: Therapeutics, Diagnostics, and Beyond
The implications of this technology span various domains within biomedicine. The ability to synthesize and screen large libraries of peptides could accelerate the development of new medications, particularly in the rapidly advancing field of peptide therapeutics. Additionally, epitope mapping—a crucial step in vaccine development—and protease/kinase substrate screening will be exponentially faster, potentially shortening the time it takes to respond to emerging diseases.
Innovations in Hardware and Software: Towards a More Integrated Synthesis Platform
EPFL’s research did not only innovate within the realm of peptide synthesis but also incorporated new hardware components and customized software. These technological advancements ensure that the process is not only efficient but also adaptable to various research requirements.
Keywords
1. High-throughput peptide synthesis
2. 384-well plate technology
3. Epitope mapping
4. Peptide library screening
5. Solid-phase peptide synthesis (SPPS)
DOI and Reference List
DOI: 10.1002/psc.3555
References
1. Muttenthaler, M., King, G.F., Adams, D.J., & Alewood, P.F. (2021). Trends in peptide drug discovery. Nature Reviews Drug Discovery, 20(4), 309-325. doi:10.1038/s41573-020-00135-8
2. Merrifield, R.B. (1963). Solid phase peptide synthesis. I. The synthesis of a tetrapeptide. Journal of the American Chemical Society, 85(14), 2149-2154. doi:10.1021/ja00897a025
3. Carpino, L.A., & Han, G.Y. (1972). 9-Fluorenylmethoxycarbonyl amino-protecting group. Journal of Organic Chemistry, 37(22), 3404-3409. doi:10.1021/jo00795a005
4. Kale, S.S., Bergeron-Brlek, M., Wu, Y., et al. (2019). Thiol-to-amine cyclization reaction enables screening of large libraries of macrocyclic compounds and the generation of sub-Kilodalton ligands. Science Advances, 5(8), eaaw2851. doi:10.1126/sciadv.aaw2851
5. Hilpert, K., & Hancock, R.E.W. (2005). High-throughput generation of small antibacterial peptides with improved activity. Nature Biotechnology, 23(8), 1008-1012. doi:10.1038/nbt1113
Conclusion
It is undeniably an exciting time for the scientific community, as the technology developed by the team at EPFL is positioned to expedite and expand the possibilities of peptide-related research. With the ability to produce and screen a massive number of peptides for biological activity, researchers are armed with a powerful tool that has the potential to usher in a new era of medical and scientific discoveries.
About the Journal
“Journal of Peptide Science” is the official publication of the European Peptide Society, providing a platform for the dissemination of major advancements in peptide science. It is an invaluable resource for researchers dedicated to the study of peptides and their applications.