Overview

Delivering on the Untapped Potential of Peptides

Ra Pharma® utilizes a process called “mRNA display” and the Extreme Diversity™ platform to produce extremely large and diverse libraries of peptides from which to screen for potential product candidates.

Ra Pharma’s platform allows us to produce synthetic macrocyclic peptides that combine the diversity and specificity of antibodies with the pharmacological properties of small molecules. The highly specific and stable peptide-like molecules generated are much smaller than monoclonal antibodies and other biologics, enabling more convenient routes of administration while still offering the opportunity to target protein-protein interactions, a type of molecular interaction that historically has been difficult to address with other small molecules. Ra Pharma believes this technology will allow us to pursue challenging targets for which only monoclonal antibodies have been developed.

mRNA Display Graphic

Step 1 — creating of peptide-mRNA fusion libraries: mRNA is translated into peptides by ribosomes using both naturally occurring amino acids and non-natural amino acids. The antibiotic puromycan is linked to each mRNA to create peptide-mRNA fusions. As a result, the translation of a relatively small amount of mRNA results in a large and diverse library of up to 100 trillion peptide-mRNA fusions.

Step 2 — creating rigid macrocycle peptides: The peptide-mRNA display libraries are then modified chemically to link two specific amino acids together and cyclize the peptide into rigid macrocycle peptides. In addition, the mRNA components of the fusions are converted to cDNA (a hybrid of mRNA and DNA) at this step.

Step 3 — selecting target peptides: Once a cyclic peptide mRNA display library is prepared, the Company selects peptides that bind to the desired target protein immobilized on the surface of a small, solid bead.

Step 4 — DNA amplification: After an initial set of peptides that bind to the target protein are selected, the Company leverages the mRNA to amplify the peptides’ corresponding DNA via a DNA amplifying technique called Polymerase Chain Reaction, or PCR.

Steps 5, 6 and 7 — repeat process to select lead candidate: The cycle can be repeated to enrich for candidate peptides (Step 5), the DNA’s sequence is determined and desired peptide candidates are synthesized based on the information in its corresponding DNA (Step 6), and candidate peptides are further screened and optimized for desired targeted binding affinity to select a lead candidate (Step 7).

Steps 5, 6 and 7 — repeat process to select lead candidate: The cycle can be repeated to enrich for candidate peptides (Step 5), the DNA’s sequence is determined and desired peptide candidates are synthesized based on the information in its corresponding DNA (Step 6), and candidate peptides are further screened and optimized for desired targeted binding affinity to select a lead candidate (Step 7).

Steps 5, 6 and 7 — repeat process to select lead candidate: The cycle can be repeated to enrich for candidate peptides (Step 5), the DNA’s sequence is determined and desired peptide candidates are synthesized based on the information in its corresponding DNA (Step 6), and candidate peptides are further screened and optimized for desired targeted binding affinity to select a lead candidate (Step 7).

If you would like to learn more about our technology, and the Extreme Diversity™ library and selection platform, please contact us at Ra-BD@RaPharma.com.