There are two main ways to synthesize peptides: chemical synthesis and biosynthesis. Chemical synthesis is mainly achieved by the condensation reaction of amino acids. In order to get the synthetic polypeptide with specific sequence, when the amino acid monomer containing functionality larger than 2 is synthesized, the group that does not need reaction should be temporarily protected.
Then the connection reaction will be carried out to ensure the synthetic orientation. The chemical synthesis of polypeptides consists of solid phase synthesis and liquid phase synthesis. The main difference is whether the solid phase carrier is used.
Peptide synthesis in liquid phase has two strategies of stepwise synthesis and fragments combination. Stepwise synthesis is used in synthesizing a variety of simple and rapid biological active polypeptide fragment; polypeptide fragment combination method containing more than 100 amino acid synthesis provides the most promising route, and has successfully synthesized a variety of biologically active peptides. Its biggest feature is easy to purify. Liquid phase synthesis method is now mainly used BOC and Z two kinds of protection methods, now mainly used in synthetic peptides, such as aspartame, L-Alanyl-L-Glutamine, oxytocin.
Compared to solid phase synthesis, it is within the protection of medium, low cost, easy to enlarge the scale of the synthesis of many advantages. Compared with solid-phase synthesis, the main drawback of liquid synthesis is that the synthesis range is small, which generally focuses on the synthesis of peptides within 10 amino acids. Besides, the intermediates need to be purified for a long time and a heavy workload. In 1963, Merrifield founded the solid phase synthesis. For this reason, Merrifield won the 1984 Nobel Prize in chemistry. The method is to fix the C end of the amino acid on the insoluble resin, and then the amino acid is condensed and the peptide chain is extended on the resin. The solid phase synthesis can be divided into BOC method and Fmoc method.
It is easy to synthesize, fast, easy to automate, and can be easily synthesized to about 30 amino acid peptides. Based on traditional liquid phase and solid phase synthesis methods, amino acid carboxylic anhydride (NCA) method, liquid phase synthesis method and combinatorial chemistry method have been developed. In the field of biosynthesis, in addition to commonly used fermentation and enzymatic hydrolysis, with the development of bioengineering technology, DNA recombination technology has also been applied to peptide synthesis.