Lead Optimization Services

Lead Optimization Services as a Route to Binding Affinity or Activity Optimization

To use a lead peptide as a full-grown therapeutic drug, its potency must increase. Tap into the knowledge of Pepscan by using our design assistance. Our epitope mapping platform can identify small peptide binders designed or derived from whole protein sequences. We can also create constrained (e.g. CLIPS™) derivatives of lead sequences with significantly improved binding activity.

Peptide Library Design Options

Pepscan offers a wide range of library design options to increase the potency of a lead peptide. Each can be tailored to address specific research questions. Find an overview below.

Alanine Scanning Libraries

Alanine scanning libraries identify residues that play a key role in peptide activity. Alanine, the smallest chiral natural amino acid, is used to substitute residues at each position of the original peptide. The effect of alanine substitution on the overall peptide activity determines the importance of each individual residue.

Combinatorial Positional Scanning Libraries

Combinatorial positional scanning libraries are an extension of the positional scanning libraries, varying systematically two or more positions at a time. These libraries allow identification of more complex effects of multiple positions on the biological activity of a peptide sequence.

Truncated Libraries

Truncated libraries are designed to systematically remove flanking residues of an active core epitope that do not contribute significantly to the binding. The 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.

Positional Scanning Libraries

Positional scanning is a key method for sequence optimization. By sequentially substituting selected amino acid residues for all other natural L-amino acids, residues crucial for activity can be identified. Substitutions displaying an improved activity can also be found.

Positional scanning library design usually starts by focusing on the naturally occurring L-amino acids. For tapping into the artificial amino acid space, non-natural amino acids can also be included. There are over 400 commercially available non-natural amino acids. Pepscan has 200 of these in stock, which can be readily implemented in your library design. We have another 300 non-natural amino acids in our database, which can be included on request.

Scrambled Libraries

Scrambled libraries screen different permutations of a specific amino acid composition. They can be used as a negative control to test the specificity of binding of a particular peptide, and thus show that its sequence is critical for activity. If the binding of a lead peptide does not show any sequence specificity, the validity of that lead peptide should be questioned.

Deletion Libraries

Deletion libraries are designed to systematically remove residues from an active core epitope that do not contribute to significantly to the binding. As with truncated libraries, the purpose of deletion libraries is also to shorten/optimize the length of the active peptide sequence.

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