Polypeptides are bioactive substances that involve various cellular functions in organisms. It is a kind of compound whose molecular structure is between amino acid and protein. It is made up of many kinds of amino acids through peptide bond in a certain order. Up to now, more than 100 kinds of peptides have been found and isolated from human body, and the research and utilization of peptides have become a prosperous scene.
Peptide synthesis customization not only has very important theoretical significance, but also has important application value. Through total peptide synthesis, we can verify the structure of a new peptide, design a new peptide to study the relationship between structure and function, provide important information for peptide biosynthesis reaction mechanism, establish model enzyme and synthesize new peptide drugs.
The chemical synthesis technology of polypeptides has been mature both in liquid phase and in solid phase. In recent decades, solid-phase peptide synthesis has become a conventional method for peptide synthesis because of its advantages of time-saving, labor-saving, material saving, easy to be controlled by computer and easy to be popularized. It has been extended to other organic matter fields such as nucleotide synthesis. In this paper, the basic principle and experimental process of solid phase synthesis are summarized, and its present situation is analyzed and the development trend in the future is prospected.
Basic principle of solid phase synthesis
Peptide synthesis is a process of repeated addition of amino acids, which is generally synthesized from C-terminal (carboxyl end) to N-terminal (amino terminal). In the past, peptide synthesis was carried out in solution. However, since Merrifield developed solid-phase peptide synthesis method in 1963, after continuous improvement and improvement, solid-phase method has become a common technology in peptide and protein synthesis, showing the incomparable advantages of classical liquid-phase synthesis.
The basic principle is: firstly, the hydroxyl group of the hydroxyl terminal amino acid of the peptide chain to be synthesized is connected with an insoluble polymer resin in the structure of covalent bond, and then the amino acid combined with the solid carrier is taken as the amino component, and then the peptide chain is extended by removing the amino protection group and reacting with excessive activated carboxyl group component.
Repeat the operation (condensation → washing → deprotection → neutralization and washing → next round condensation) to reach the length of peptide chain to be synthesized, and then the peptide chain will be split off from the resin and purified to obtain the desired peptide.
Among them, the BOC solid state synthesis method is called when α - amino group is protected by BOC (TERT butoxycarbonyl) and Fmoc (9-fluorene methoxycarbonyl) is used to protect α - amino group
