Peptide synthesis is a solid-phase synthesis sequence from the N-terminal (ammonia terminal) to the C-terminal (carboxyl terminal). In the past, peptide synthesis was carried out in solution, which is called liquid phase synthesis. Since Merrifield successfully developed the solid-phase peptide synthesis method in 1963, through continuous improvement and improvement, the solid-phase method has become a common technology in peptide and protein synthesis, showing the incomparable advantages of the classical liquid-phase synthesis method, thus greatly reducing the difficulty of product purification in each step. Generally speaking, peptide synthesis can be divided into two types: solid-phase synthesis and liquid-phase peptide synthesis.
Definition of polypeptide
Polypeptide is a kind of bioactive substance related to various cell functions in organism. Its molecular structure is between amino acids and proteins. It is a compound composed of many kinds of amino acids combined by peptide bond in a certain order. Polypeptides are the general term of bioactive substances related to various cell functions in organisms, which are often used in functional analysis, antibody research, especially in drug research and development.
In 1963, Merrifield first proposed the method of solid-phase peptide synthesis (SPPs). Because of its convenient and rapid synthesis, it became the preferred method of peptide synthesis, and brought a revolution in peptide organic synthesis, and became an independent discipline solid-phase organic synthesis. The invention of solid-phase synthesis promoted the automation of peptide synthesis at the same time. The first real peptide synthesizer in the world appeared in the early 1980s.
Peptide synthesis technology
In 1963, Merrifield first proposed the method of solid-phase peptide synthesis (SPPs). Because of its convenient and rapid synthesis, it became the preferred method of peptide synthesis, and brought a revolution in peptide organic synthesis, and became an independent discipline solid-phase organic synthesis. The invention of solid-phase synthesis promoted the automation of peptide synthesis at the same time. The first real peptide synthesizer in the world appeared in the early 1980s.
solution-phase synthesis
Based on adding a single n-α protected amino acid to the growing amino acid repeatedly, the synthesis proceeds step by step, usually starting from the C-terminal amino acid of the synthesis chain, and then the connection of the single amino acid is realized by using DCC, mixed carboxyanhydrides or N-carboxyanhydrides.
The carbodiimide method includes using DCC as a linker to connect n – and C-protected amino acids. It is important that the linker can promote the shrinkage between the carbon group of N-protected amino acid and the free amino group of C-protected amino acid to form peptide chain, and at the same time produce n, n? / font > – dyaylcohercylurea by-product.
However, this method is affected by the side effects of racemization or the formation of 5 (4h) – oxaylones and n-acylurea in the presence of strong bases. Fortunately, these side effects can be minimized, but not eliminated completely. In addition, the method can also be used to synthesize the active ester derivatives of N-protected amino acids. The active ester produced in turn will spontaneously react with any other C-protected amino acid or peptide to form a new peptide
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