Total Peptide Library: More Flexible and Productive


Peptides with low molecular weight have been known to be less allergenic and the diverse physiological roles of peptides make them suitable candidates for the development of therapeutic agents. Peptide drugs are widely used in the prevention, diagnosis, and treatment of diseases such as cancer, diabetes, and AIDS. However, the development of peptide drugs is not smooth because of the difficulty in peptide drug discovery and the lack of special peptide libraries.

 

Peptide libraries, which contain a great number of peptides that have a systematic combination of amino acids, are widely applied as a powerful tool for screening large numbers of peptides in the search for critical bioactive peptides in biological research, protein-related study, and drug development. Given its significance, several methods have been developed to construct peptide libraries. These peptide library constructions involve the use of synthetic chemistry tools and biotechnological approaches.

 

Traditionally, it was found that the success of phage-derived peptides essentially depends on the quality of the library screened, however, there is no practical method to monitor or guarantee the quality of the phage display library. Indeed, until now only a few of the peptides selected by phage display have entered clinical applications. Based on the solid phase synthesis developed by Merrifield, the combinatorial "split-mix synthesis" method was developed for peptide library construction. Theoretically, a huge number of peptides can be synthesized in this way to make a large library, however, in practice, the number of the peptides synthesized in this way is limited due to the high cost and low production yields of synthesizing the library.

 

At present, peptide libraries can be constructed by synthesizing a large number of distinct peptides. Since there is no good way to predict which peptide will be a good drug candidate, it is desired to construct a large peptide library, which contains all possible combinations of the amino acids, for a high chance of finding good drug candidates during peptide screening. Large peptide libraries may contain thousands to millions of peptides but, the size of the library is often inversely related to the control over each peptide sequence. The techniques that are suitable for large library constructions are much less flexible in designing the sequence of each entity in the library. Therefore, the larger library capacity complicates the synthesis of peptide drugs and becomes a barrier to the development of peptide drugs.

 

To overcome this obstacle, experts have developed a versatile peptide design platform that is equipped with peptide information compression technology. Researchers use bioinformatics methods to compress peptide information, which can integrate the information of multiple peptides into one peptide, thereby containing a large amount of peptide information in a relatively small storage volume. Based on this technology, scientists have constructed a total peptide library, containing nearly 500 million different peptide sequence information in a library of approximately 80,000 peptides, which will increase the screening efficiency by approximately 6,000 times.

 

Since the peptide library provides a powerful tool for drug development, protein-protein interactions, and other biochemical as well as pharmaceutical applications, the total peptide library becomes a productive tool as it enjoys higher stability because of the special structure of the peptide bond. Additionally, its construction cycle is relatively short compared with traditional peptide library construction technologies, accelerating the development of peptide drugs. 

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