Peptide Knowledge Center

Synthesis of Peptide Molecules Based on Liquid Phase Technology

At present, chemists and special researchers actively participate in the research and development of peptide drugs, and put forward constructive opinions on the application of liquid phase technology from the perspective of clinical medicinal value, so as to promote the full clinical role of peptide drugs.

During this period, liquid phase peptide synthesis technology provides reliable technical support for purification of peptide separation, protein synthesis and other content. Nowadays, liquid phase technology has been transferred from laboratory to industrial production and has become an effective separation technology within the scope of biotechnology. 

In order to study the synthesis content of peptide drugs, this paper uses liquid phase technology to design the synthesis route of peptide drugs, and successfully obtains the raw materials, which provides a reference for in-depth research.

Overview of Peptide Synthesis by Liquid Phase Method

The practice of synthesizing peptide drugs by liquid phase technology is not achieved overnight. To continue to achieve remarkable results, a reasonable and feasible liquid phase synthesis plan must be formulated. When starting to plan the synthesis, the utilization strategy of the synthesis method should be analyzed first, such as general chemical synthesis, especially linear or phase inversion synthesis, selection of fragments and assembly of these fragments, reasonable application of orthogonal strategies, etc. we can check Omizzur custom peptide synthesis about peptide synthesis technology.

When the method is relatively mature, it is also necessary to pay attention to the particularity of the method, not only to solve the chemical technical problems, but also to meet the requirements of the regulatory authorities. The above factors need to be considered in pharmaceuticals.

Advantages of peptide liquid phase segmented synthesis method

Liquid-phase synthesis is another major breakthrough in the field of peptide and protein synthesis, that is, a synthetic method in which peptide fragments are spontaneously connected to grow peptides in solution according to their chemical specificity or chemical selectivity. Because the peptide fragment contains relatively few amino acid residues, it has high purity and is easy to purify.

Liquid Phase Peptide Synthesis Analysis

1 Amino protection

In liquid phase synthesis, tert-butoxycarbonyl (Boc) and benzyloxycarbonyl (Z) have certain utilization values. In contrast, the application rate of the Fmoc group in liquid-phase peptide synthesis is relatively low. The reason is that the dissolution effect of by-products is poor and the reaction speed slows down. It should be noted that tert-butoxycarbonyl (Boc) is used in conjunction with acid removal and ethyl acetate reagents. Generally, hydrochloride substances are in solid form, which increases the probability of separation. The removal of the Z group is usually a selective reduction method, using a catalyst to complete the catalytic hydrogenolysis, and liquid ammonia can also be used for the reduction reaction.

2 Carboxyl protection

Currently, many peptides exist as C-terminal amino compounds, eliminating the need to protect the carboxyl group. In the process of protecting the effect, in order to obtain the orthogonal effect of the protecting group, it is extremely necessary to effectively use the benzyl or tert-butyl ester group. If aliphatic esters are used, the protection method is a saponification reaction with NaOH or KOH. Although there is a risk of racemization, which reduces the reaction efficiency, it can be converted into hydrazine salt by hydrazine treatment. In the azide method, hydrazine salt can be directly condensed.

Design of liquid phase synthesis of peptide drugs

According to statistics, the incidence of breast cancer is increasing year by year, and the mortality rate of this type of cancer is relatively high, which leads to a negative state for patients and their families. With the increase in the incidence of breast cancer, the demand for Norad in the international market has also increased accordingly, and the price of Norad is expensive. Therefore, the research on the liquid phase synthesis of Norad has certain practical significance.

Synthetic route design

In one aspect, the fragment condensation method (4+6 fragment condensation method) is preferred. That is to determine the position of the disconnected fragment, provide it with the necessary methyl ester protection, and complete the methyl ester removal task through the azide method. On the other hand, short peptide fragments are subdivided, and the required target polypeptides are obtained through operations such as peptide fragment synthesis and condensation. For comprehensive analysis, the target compound should be divided into two fragments.

Peptide fractional synthesis technology is one of the effective ways of peptide synthesis and plays a pivotal role in the field of peptide synthesis. Natural chemical ligation is the basic method of fragmented peptide synthesis, and it is also the most widely used peptide synthesis method at present.

Summary and Outlook

Generally speaking, the peptide synthesis technology is not perfect enough, and there are still some problems in the field of peptide synthesis. For example, temperature can change the conformation of polypeptides, how to adjust the temperature to achieve the best condensation effect; how to minimize racemization during the synthesis process; find better solvents and condensing agents to improve the condensation rate. Research and explore further.