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Macrocyclic peptides are a kind of promising compounds. They can usually participate in challenging therapeutic targets by using their large binding interface to interact with binding partners. Display technology, such as mRNA display, allows the effective discovery of macrocyclic peptides. CD Biosynsis has been committed to the research of peptides and proteins for many years. The high-throughput peptide discovery platform based on its mRNA display technology can provide customers with the development services of macrocyclic peptides.
Unlike traditional small-molecule therapies, macrocyclic peptides (cyclic peptides containing 12 or more member rings) can participate in challenging targets because they use large binding interfaces to interact with binding partners, similar to natural protein-protein interactions. When combined with their limited conformational flexibility (the result of cyclization), this can give them high selectivity and affinity for binding interaction. For these reasons, macrocyclic peptides are usually used to bind to the target reserved by monoclonal antibodies; However, compared with antibodies, they have obvious advantages, including easy synthesis and modification, which may reduce production costs, and in some cases, they can replicate the properties of small molecules of drugs. In the past decade, on average, a new macrocyclic peptide drug has entered the market every year.
Fig. 1 Representative Examples of Macrocyclic Peptide Hits. (Peacock H, et al., 2021)
Macrocyclic peptides can be found by screening and guiding methods, without initial knowledge of the target structure or potential binding conformation of ligands, and only rely on the diversity of a large number of candidate ligands (called libraries) to find optimized binders. MRNA display is a screening method. This process starts from a random DNA sequence library. The library is transcribed into mRNA by the action of enzyme RNA polymerase, and then the mRNA library is connected to the molecular puromycin and translated in vitro. To construct a macrocyclic peptide, the cyclization step is inserted. At this time, the mRNA tag is usually reverse transcribed to produce a library of mRNA/cDNA – puromycin-peptide conjugates. Then there is a simple target screening process. After multiple cycles, macrocyclic molecules with high affinity and specificity can be obtained.
The peptide discovery platform based on mRNA display technology of CD Biosynsis can obtain a large-capacity macrocyclic display peptide library by constructing a random DNA sequence library, after in vitro transcription and translation, and introducing macrocyclic modification by means of various cyclization strategies, and then conducting drug target screening and multiple rounds of cyclic screening to obtain high-affinity macrocyclic peptides. We can provide customers around the world with a variety of one-stop services for the development of macrocyclic peptides, saving your valuable time and allowing your energy to only focus on the key project processes.
Cyclization Strategies:
In our macrocyclic peptide development service, you only need to provide your project requirements or lead peptide sequence, and then our experts will tailor the most appropriate project plan for you.
CD Biosynsis has many years of project development experience in peptide discovery. Based on the mRNA display technology platform, it can provide customers with macrocyclic peptides development services. If you are interested in our services, please contact us for more details.
Reference
Peacock, H., & Suga, H. (2021). Discovery of De Novo Macrocyclic Peptides by Messenger RNA Display. Trends in Pharmacological Sciences, 42(5), 385–397.
