Peptide pool is a group of immunostimulatory antigen clusters, which is a collection of a large number of small peptides of specific length and different sequences. It includes the permutation and combination of various (or most) amino acid sequences in the short peptide of this length. Peptide pool is a powerful tool in biological research, which can be used to screen a large number of peptides to find a few key biologically active peptides. It can be used in drug design, protein-protein interaction, biochemistry and drug application, etc. At the same time, it also has a wide range of applications in drug screening, target determination, epitope mapping, and vaccine development.

The peptide pool was first proposed by Geyson and his colleagues in 1986. They believed that: (1) The binding or recognition between protein molecules is mainly completed by the interaction between several amino acid residues on the partial peptide, and these amino acids form a non-covalent bond connection; (2) although some peptides have different sequences from the natural epitope of the antigen, they bind antibodies or ligands in the same way. Therefore, such peptides with key amino acid residues are called mimotopes. The concept of mimotopes played an important role in the development of random peptide pools.

Application of peptide library

1. Research on protein folding and three-dimensional structure prediction

Gething conducted research on protein folding. Researcher used an octapeptide library and Bip (immunoglobulin heavy chain-binding protein) as a model, and she has obtained preliminary results. The formation of protein spatial conformation starts from the mutual recognition of peptides (usually hexapeptides). The peptide library is used to study the mutual recognition of peptides, which provides experimental basis for the theoretical prediction of protein spatial conformation.

2. Molecular recognition

Molecular recognition includes many aspects, and the research in these aspects is currently the most. Common applications include mutual recognition between antigens and antibodies, mutual recognition between hormones and receptors, recognition between protein and DNA, and mutual recognition between protein and non-protein (such as avidin). Some people have used peptide library technology to screen and get liver cancer cell epitope peptide HCBP1 (FQHPSFI), hepatocellular cancer antibody binding peptide XC24p11, and liver cancer serum marker binding peptide HC1 (RGW-CRPLPKGEG). These polypeptides can be used to identify tumor surface markers, so that they can be developed as peptide probes for early cancer diagnosis.

3. Application prospects in enzyme engineering

At present, the application of peptide library technology in enzyme engineering is still relatively small. However, the application potential of peptide library technology in enzyme engineering is great. It can be used to screen enzyme inhibitors, activators, stabilizers, etc. Combined with X-ray diffraction technology and rapid reaction kinetics technology, it is possible to further study the mechanism of enzyme and substrate interaction, and the relationship between structure and function. In addition, it has great reference and guidance for enzyme modification, transformation, artificial enzyme design, protein engineering, etc.

4. Application prospects in other fields

Since peptide library technology has just started, many fields have not yet been developed, and its huge application potential has not been fully utilized. Work in these fields is urgently needed.

4.1 Drug design: such as receptor inhibitors, activator screening, hormone analogue screening (such as enkephalin analogues). The selected peptide fragments can be used directly as drugs, or they can be modified or referenced to their structure to synthesize organic drugs.

4.2 Disease detection: Some diseases are often accompanied by the production of special proteins, such as autoantibodies for autoimmune diseases, HIV antibodies for AIDS, etc. The screened peptides can be used as generation antigens for ELISA detection. Sarhin used peptide library technology to screen out two peptides DE532 (VETSQYFRGTLS) and DE-Obs (HNDLFPSWYHNY) that specifically bind to MKN-45 cells. These two peptides can be used as potential carriers for the diagnosis and treatment of gastric cancer.

4.3 Disease treatment: For some diseases with relatively clear pathology, the selected peptides can be used to block an intermediate link of the disease. For example, AIDS, HIV must infect CD4 cells to destroy the human immune system. Use peptides or their analogs that have a strong affinity for HIV to block the combination of HIV and CD4 cells, thereby blocking the destruction of the human immune system by HIV.

References

  1. Gething M J, Sambrook J. Protein folding in the cell[J]. Nature, 1992, 355(6355): 33-45.
  2. Zhang B, Zhang Y, Wang J, et al. Screening and identification of a targeting peptide to hepatocarcinoma from a phage display peptide library[J]. Molecular medicine, 2007, 13(5): 246-254.
  3. Hwang H M, Heo C K, Lee H J, et al. Identification of anti-SF3B1 autoantibody as a diagnostic marker in patients with hepatocellular carcinoma[J]. Journal of translational medicine, 2018, 16(1): 1-16.
  4. Zhang Z, Xu L, Wang Z. Screening serum biomarkers for early primary hepatocellular carcinoma using a phage display technique[J]. Journal of clinical laboratory analysis, 2011, 25(6): 402-408.
  5. Sahin D, Taflan S O, Yartas G, et al. Screening and identification of peptides specifically targeted to gastric cancer cells from a phage display peptide library[J]. Asian Pacific journal of cancer prevention: APJCP, 2018, 19(4): 927.