mRNA Display-based Stapled Peptide Development

The difference between the synthesis of stapled peptides and the synthesis of ordinary peptides is that two unnatural amino acids containing α-methyl and α-alkenyl groups are introduced during the synthesis of peptide chains, and then olefin metathesis reactions occur between the two unnatural amino acids, thereby generate α-helical stable all-carbon scaffolds and further synthesize staple peptides. CD BioSciences is working to develop a strategy to incorporate this AA into in vitro translated peptide library, opening access to mRNA-displayed peptide libraries for the discovery of novel staple peptides.

Introduction into Stapled Peptide

Stapled peptide is based on the formation of polypeptide α-Helixes are developed on the demand of entering cells through cell membranes. The regulation of various life processes in organisms is achieved through the interaction between protein and protein (PPI). Usually, the interface of PPI is too large, which makes it difficult for small molecular drugs to target them, so as to effectively and specifically block this interaction and show good therapeutic effect. Protein drugs can not directly target intracellular interactions because they are difficult to pass through the cell membrane. Research shows that there are α-Helical structure and positively charged peptides can pass through the cell membrane. A method of stabilizing the α-helical structure of polypeptides using C-C bonds as a scaffold has been developed, and the peptides obtained by this method are called stapled peptides. Stapled peptide has a higher degree of α-helix, strong binding ability, can pass through the cell membrane, is difficult to be hydrolyzed by protease, and has a long half-life in vivo.

Fig. 1 A mock selection cycle using stapled mRNA display to measure enrichment of E2 binding peptide 10. (Iqbal E., et al., 2019)

mRNA Display for Development of Stapled Peptide

There have been some efforts to create stapled peptide libraries, but so far, the diversity of these libraries is limited to about 100 unique peptides. It is very exciting to use in vitro selection strategies (such as mRNA display) to create stapled peptide libraries, because these libraries provide the ability to create up to 10¹³ members. In addition, mRNA display allows the direct binding of non-standard amino acids (ncAAs) into the peptide library to further optimize and enhance the affinity. Studies explored the properties of α-methyl-containing Cys (a-MeCys)-constrained peptides and developed a system for incorporating a-MeCys into an mRNA-displaying peptide library for the discovery of PPI inhibitors.

Our Services

CD BioSciences has always adhered to the business philosophy of "customer first", continuously optimized the development conditions and purification process through long-term experimental accumulation, and has developed a mature development process of stapled peptides, and has the development ability to provide high-quality stapled peptides to the world, which can fully meet the various research and development needs of customers.

• The peptide discovery platform based on our mRNA display technology can be constructed by constructing a random DNA sequence library and transcribing it in vitro, and then introducing the α- non-natural amino acids of the group are transferred to the peptide library for translation, so as to develop a variety of uses, especially the bookbinding peptide for PPI research.
• In our stapled peptide development service, you only need to provide specific requirements for your project, and then our experts will customize the most appropriate project plan for you.

Services Features

• Advanced display technology can quickly shorten the experimental period.
• The professional technical team can accurately control the project process.
• Flexible private customized service, close to the cutting-edge research of customers.
• High-quality result report helps to find the target quickly.

CD BioSciences has many years of project development experience in peptide discovery. Based on the mRNA display technology platform, it can provide customers with stapled peptides development services. If you are interested in our services, please contact us for more details.

Reference

1. Iqbal, E. S., Richardson, S. L., Abrigo, N. A., et al. (2019). A new strategy for the in vitro selection of stapled peptide inhibitors by mRNA display. Chemical communications, 55(61), 8959–8962.

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