Glycopeptide application is not a dream, artificial synthesis has achieved break

Recently, the top journal in the field of chemistry "Angew.Chem.Int.Ed." published a commercial peptide synthesizer and chemical enzymatic method jointly completed by the Wen Liuqing research group of the Shanghai Institute of Materia Medica, Chinese Academy of Sciences and Professor Wang Peng of Southern University of Science and Technology. Research report on the synthesis of glycopeptides with complex oligosaccharide structure.

Researchers have screened a large number of solid-phase supports that can be used for solid-phase synthesis and found a silicon sphere with only amino groups on the surface that can be used for both organic phase peptide synthesis and aqueous phase oligosaccharide synthesis. The chemical peptide synthesizer has developed a system that includes a two-phase reaction. After multiple cycles of successive reactions between the organic phase and the water phase, the target glycopeptide can be obtained.

Therefore, the researchers realized the semi-automatic synthesis of 13 kinds of complex glycopeptides based on the commercial peptide synthesizer, and the research results also provided a feasible scheme for the synthesis of glycopeptides.

What is glycopeptide?

Glycopeptides are macromolecular compounds that combine oligosaccharides and polypeptides. According to the different glycopeptide bonds, they can be divided into two types: N-glycopeptide bonds and O-glycopeptide bonds.

N-glycopeptide bond refers to the N-glycosidic bond formed by covalently linking the β-configuration N-acetylglucosamine anomeric carbon and the γ-amide N atom of asparagine;

O-glycopeptide bond refers to an O-glycosidic bond formed by covalently bonding the anomeric carbon of a monosaccharide and the hydroxyl O atom of a hydroxyl amino acid.

As glycopeptides play an important role in various physiological and pathological functions of animals and plants, they have always been a hot topic in the research field.

The earliest application of glycopeptides appeared in the field of medicine as Antibiotics, and Vancomycin is a typical glycopeptide antibiotic.

Vancomycin was first isolated by ECKornfeld from the soil deep in the Borneo jungle collected by a missionary, and it was found to have significant antibacterial effects. It was used to treat infections caused by penicillin-resistant Staphylococcus aureus. Because of its excellent resistance to drug resistance, the US FDA granted its application permission in 1958. Its mechanism of action is to inhibit the synthesis of bacterial cell walls and have a bactericidal effect. In addition, it can also change the permeability of bacterial cell membranes and hinder the synthesis of bacterial RNA.

Diversification of glycopeptides blocked

The function of glycopeptides is far more than just antibacterial. Many studies have confirmed that glycopeptides have active effects such as improving immunity and improving human functions.

However, the different structures of glycopeptides exhibit different functional properties. Due to the limitation of sources, it is difficult to meet diverse needs, and synthesis has become an important way to expand channels. At present, the synthetic methods of glycopeptides include chemical synthesis, enzymatic synthesis and chemical enzymatic synthesis, but most of these methods are cumbersome in procedures, difficult to purify, and cannot be targeted for synthesis. It is difficult to achieve the needs of industrial production, which also makes the application of glycopeptides only limited. In terms of drugs, the health care product market with greater prospects is still blank.

Currently, glycopeptides are mainly obtained through microbial fermentation and plant extraction, such as:

Vancomycin antibiotics are extracted by fermentation of Amycobacterium orientalis or Actinomycetes;

Mannan peptides are present in the capsule and culture medium of Streptococcus hemolyticus;

Yunzhi intracellular glycopeptide is extracted from medicinal fungi. It has pharmacological activities such as immune enhancement, liver protection and auxiliary cancer treatment.

In terms of functional foods, the application of glycopeptides is very limited. After inquiry, there is only one glycopeptide health food approved at present, which is Yunzhi glycopeptide product approved in 2000.

Functional glycopeptide

Polysaccharides are the active ingredients in many plants and are also popular ingredients in functional foods. According to the types of monosaccharides, polysaccharides can be divided into homopolysaccharides, heteropolysaccharides, glycoconjugates, etc., among which glycoconjugates refer to the combination of polysaccharides and other non-sugar moieties such as proteins, polypeptides, lipids, etc. There are certain glycopeptide components in many polysaccharide products, and we can consider extracting such components to give full play to their functional properties. At present, two kinds of wolfberry glycopeptide and natto glycopeptide are expected to be used in functional foods.

Lycium barbarum glycopeptide

Public information shows that the market size of China's goji berry industry in 2018 was 15.453 billion yuan, an increase of 8.7% year-on-year. It is expected that by 2020 its market size will grow to about 18.303 billion yuan. Goji berry is widely consumed by the world due to its high quality and low price. Loved by them.

Lycium barbarum polysaccharide is the main active component of Lycium barbarum, and Lycium barbarum glycopeptide is further separated and purified from Lycium barbarum polysaccharide to obtain 5 glycoconjugates with strong immunological activity. Pharmacological experiments show that its immune performance is 10-20 stronger than that of Lycium barbarum. Times. The polysaccharide content in Lycium barbarum glycopeptide is 70%, the sugar composition is ArA:GAl:GlC=2.5:1.0:1.0 (molar ratio), and contains other 17 kinds of natural amino acids, which can improve immunity, protect the liver, improve eyesight, and strengthen Kidney, anti-aging, lowering blood pressure, lowering blood fat, treating cancer, enhancing hematopoietic function, beautifying and beautifying.

Natto glycopeptide

Natto is one of the most popular health foods. In 2019, the market size of natto and natto-related products in my country is about 256 million yuan. It is estimated that the domestic market demand will reach nearly 300 million yuan in 2020. Natto is popular because it contains polysaccharides, peptides, Nattokinase and other active ingredients. In recent years, it has been found that natto also contains more active natto glycopeptides. Modern research points out that part of the glycopeptides in natto are produced by fermentation, and the other part is derived from natto bacteria. Among them, the glycopeptides in natto bacteria are considered to be the main active ingredients, which have been shown to be significant in animal experiments. The immune enhancement effect.

At present, the cost of extracting glycopeptides from natural animals and plants is relatively high. Even as a health food, the effective amount needs to be defined, which virtually increases the price of the product and is not conducive to market development.

For example, Lycium barbarum glycopeptide, although its effect is more obvious, it is still unknown whether the cost increase brought by consumers can "pay the bill". From the perspective of profit, it is better to choose the wolfberry polysaccharide which is more obvious to the audience.

If the synthetic glycopeptide can be implemented smoothly, it will not only reduce product costs, but also increase market acceptance, and it will also be conducive to the continuous improvement of forced policies. From the perspective of market and top-level design, the success of synthetic glycopeptides is of great significance.