Biology:Peptide library

A peptide library is a tool for studying proteins. Peptide libraries typically contain a large number of peptides that have a systematic combination of amino acids. Usually, the peptide library is synthesized on a solid phase, mostly on resin, which can be made as a flat surface or beads. The peptide library is a popular tool for drug design, protein–protein interactions, and other biochemical and pharmaceutical applications.

Synthetic peptide libraries are synthesized without utilizing phage or other biological systems. There are at least five subtypes of synthetic peptide libraries that differ from each other by the method which was used for the synthesis of the library. The subtypes are:

• Overlapping peptide libraries
• Truncation peptide libraries
• Random libraries
• Alanine scanning libraries
• Positional or scrambled peptide libraries.

This form of peptide synthesis is limited to a peptide chain length of approximately 70 amino acids and is generally unsuitable for the study of larger proteins. For 20 amino acids, this results in an upper limit of 20⁷⁰ possible combinations, not considering the plethora of available amino acids with pre-installed post-translational modifications. From this number of total combinations, the scope of the peptide library can be narrowed down for a more specific purpose by selecting which amino acids are desired at each point in the chain.

For example, a peptide chain of 10 residues in length is used in native chemical ligation with a larger recombinantly expressed protein.

• Residue 1: alanine
• Residue 2: one of glutamine, glycine, arginine, glutamic acid, serine, or methionine
• Residue 3: any one of the 20 amino acids
• Residue 4: acetyllysine
• Residue 5: alanine
• Residue 6: isoleucine
• Residue 7: aspartic acid
• Residue 8: phenylalanine
• Residue 9: acetyllysine
• Residue 10: arginine with the carboxy terminal thioester

With 7 possibilities at Residue 2 and 20 possibilities at Residue 3, the total would be [math]\displaystyle{ 20\times7 }[/math] or 140 different polypeptides in the library.

This peptide library would be useful for analyzing the effect of the post-translational modification acetylation on lysine which neutralizes the positive charge. Having the library of different peptides at residue 2 and 3 would let the investigator see if some change in chemical properties in the N-terminal tail of the ligated protein makes the protein more useful or useful in a different way.

Large random peptide libraries are often used for the synthesis of certain peptide molecules, such as ultra-large chemical libraries for the discovery of high-affinity peptide binders, and an increase in the library size severely affects parameters, such as the synthesis scale, the number of library members, the sequence deconvolution and peptide structure elucidation. To mitigate these technical challenges, an algorithm-supported approach to peptide library design may use molecular mass and amino acid diversity to simplify the laborious permutation identification in complex mixtures when using mass spectrometry. This approach is used to avoid mass redundancy.

Some companies, such as Pepscan and GenScript, manufacture customized peptide libraries.

Further reading

• Peptide library at pbcpeptide.com