Peptide library

A peptide library is a tool for protein related study. A peptide library contains a great number of peptides that have a systematic combination of amino acids. Usually, peptide library is synthesized on solid phase, mostly on resin, which can be made as flat surface or beads. The peptide library provides a powerful tool for drug design, protein-protein interactions, and other biochemical as well as pharmaceutical applications.

You can create a mix of desired amino acids at each point in a sequence. In this way, you could create a library of 20 different polypeptides with only one amino acid residue at random and the rest being the same.

The usefulness of this form of peptide synthesis is limited as you can't go beyond 70 acids in length. This would give you 20⁷⁰ possible combinations and that's only if you don't include the plethora of available amino acids with pre-installed post-translational modifications. Most drug development does not involve such a random assortment of proteins as you wouldn't learn very much.

Important example. Say you wanted a peptide chain 10 residues in length to use in native chemical ligation with a larger recombinantly expressed protein.

• Chosen out of complete randomness*you want a set of proteins with the following.

residue 1: Alanine only residue 2: glutamine, glycine, arginine, glutamic acid, serine, or methionine residue 3: any one of all 20 amino acids residue 4: acetyl-lysine only residue 5: alanine residue 6: isoleucine residue 7: aspartic acid residue 8: phenylalanine residue 9: acetyl-lysine residue 10: argineine with the carboxy terminal thioester.

there would be 20 different proteins at residue 3. each one of those would have 7 different proteins at residue 2. the end result would be 20*7 or 140 different polypeptides. 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 you see if some change in chemical properties in the N-terminal tail of the ligated protein make the protein more useful or useful in a different way.

As a general formula, if you made a completely random peptide library with n amino acids for each link in the chain with a length of x, the total number of possible sequences is n^x.

Design tools

There are free online software to design peptide libraries with the ability to generate large numbers of screening peptides.

1. Overlapping Peptide Library: The generation of peptide library by breaking the original protein or peptide into many equal-length overlapping fragment and it is used for linear, continuous epitope mapping and T-cell epitope determination.
3. Alanine Peptide Scanning Library: The generation of peptide library in which alanine (Ala, A) is systematically substituted into each of the amino acids which can be used to identify epitope activity.
5. Positional Peptide Library: A selected position in a peptide sequence is systematically replaced with different amino acid to show the effect on the substitute amino acid at certain position.
7. Truncation Peptide Library: The truncation library has been used to predict the minimum amino acid length required for optimum epitope activity.
9. Random Peptide Library: It's constructed by substituting selected positions on the original peptide randomly and simultaneously with all other natural amino acids in a shot gun approach with a purpose to elucidate potential alternatives for enhanced peptide activity.
11. Scramble Peptide Library: Scramble Library is constructed by carrying out permutation on the original peptide's sequence. It has the potential to give all possible alternatives and offers and represents the highest degree of variability for peptide library.
13. T-cell Truncated Peptide Libraries: Allow the testing of all possible T-cell epitopes across a protein of interest.

References

• Peptide library at pbcpeptide.com
• Peptide library design tools at biosyn.com