Naturals replacement scans and validation
Custom-made libraries to optimize your therapeutic peptide lead
The majority of peptides identified as lead or candidate-lead in a screening campaign display interesting yet suboptimal properties for use as a full-grown therapeutic drug. Typical affinities to the target protein are usually in the (sub)micromolar range, while the stability to proteolytic degradation is yet insufficient; this, alongside in-vivo half-life and bioavailability, should be optimized. Each of these, however, requires a different and separate program, as mutations optimizing the affinity to a certain target protein do not have the same benefits for stability, biodistribution or half-life extension.
We have many years of experience in peptide-lead optimization at Pepscan. Our highly skilled project teams are well-equipped to bring a candidate peptide drug to the next level. We can support you in designing the most efficient and economical library and help you compute lists of peptide library sequences. If the 3D conformation of your peptide is crucial, we also offer unique libraries of 3D-constrained (CLIPS) peptides. A wide range of library design options are available and each is tailored to address your specific research questions.
Peptide library design options
Alanine scanning libraries are used to identify residues that play a key role in the activity of a peptide. Alanine, the smallest chiral natural amino acid, substitutes residues at each position of the original peptide. The effect of alanine substitution on overall peptide activity determines the importance of each individual residue.
Scrambled libraries are used to screen permutations of a specific amino acid composition or as a negative control for a specific peptide to show that its sequence is critical for activity.
Truncated libraries are designed by systematically removing flanking sequences of an active sequence core. Their purpose is to identify the shortest amino acid sequence needed for activity. If the essential amino acids have been identified by alanine scanning or other technologies, truncations can be tailored around these key amino acid residues.
T-cell truncated peptide libraries are a combination of overlapping and truncated library design, allowing high-resolution identification of T-cell epitopes. Equimolar mixtures of the four C-terminal peptides for each nominal 11-mer are provided in each tube (i.e. all 8 to 11-mers). The results are analyzed to obtain precise epitope identification with significantly fewer assays compared to overlapping peptide libraries.