Spatially Defined Peptide Constructs
The addition of new technologies to custom peptide tools is allowing companies to carve their own niches in a market that is being flooded by me-too players. Like many custom peptide businesses, Pepscan’s peptides research business, Pepscan Presto, offers a range of peptide tools, including custom peptides and custom, kinase and protease PepChip microarrays. The company is also exploiting its CLIPS™ (chemically linked immunogenic peptides on scaffolds) technology, for the design and construction of peptides with spatially defined structures.
“Generally, when you take a peptide out of its large protein context it simply doesn’t fold into the correct 3-D structure,” explains Peter van Djiken, Ph.D., chief commercial officer. “This means the peptide doesn’t represent a true copy of the protein domain it’s derived from.
“Our CLIPS technology solves such problems by constructing conformationally correct peptides that mimic small parts of the native protein. As a result, CLIPS peptides are highly suitable for identifying and reconstructing complex protein interaction sites. The technology also improves the function of bioactive peptides 5- to 20-fold compared with ordinary peptides. Potential applications are manifold, including complex epitope mapping, raising monoclonal antibodies, and vaccine development.”
The CLIPS technology involves attaching small organic template molecules to anchor points incorporated at specific locations on the peptide sequences as it’s constructed. The templates induce the peptide to fold into desired loop, helix, or even sheet-like conformations.
“It’s a toolbox we can use to make all kinds of specially defined molecules,” Dr. van Djiken claims. “Advantages of the CLIPS technology include its simplicity—it is a one-step addition reaction carried out after coupling the last peptide, and its high-yield, which can reach 100%. This makes it suitable for highly parallel synthesis of large combinatorial libraries of both soluble and solid-phase bound compounds.”
It’s also a useful tool for raising antibodies against target proteins that cannot be generated recombinantly, he suggests. “Membrane-spanning proteins such as GPCRs and ion channels are hard to reproduce because they don’t fold correctly out of the context of the lipid bilayer. With CLIPs, however, we can generate peptides that accurately mimic extracellular loops from transmembrane proteins, and use these to raise antibodies that fully cross-react with the native target.”
The CLIPS approach can be applied to any synthetic peptide, including modified or long peptides of 80 amino acids in length or greater, Dr. van Djiken says.