Synthesis techniques of long-refractory peptides

Synthesis techniques of long-refractory peptides

In the study of peptide synthesis, solid-phase peptide synthesis is the most widely used method. In the process of long peptide synthesis, with the extension of peptide chain, the reaction will gradually become more difficult, and some target peptides without residues will be produced.These peptide chains are also the main impurities in the synthesis of long peptides.Therefore, in the process of long peptide synthesis, we need to overcome the main difficulty is to explore better reaction conditions and methods, so as to make the amino acid condensation reaction more fully and thoroughly.At the same time, the reaction time is shortened, because the longer the reaction time is, the more uncontrollable side reactions are, and the more complex the by-products are. These by-products are also important components of impurities produced in the whole reaction.Due to various factors, the condensation reaction of amino acids is relatively difficult, and the traditional sequential condensation can not meet our requirements for peptide quality. After long-term experiments and exploration, in order to reduce the occurrence of side reactions and by-products, and improve the quality of peptides, our company has further improved the synthesis technology of long and difficult peptides, and has successfully synthesized more than 200 amino acid peptides.

For the long-term peptide, we take the following measures:

(1)Fragment peptide synthesis method:

When the length of peptide chain is long and the requirement is high, the traditional method of gradual extension can not meet the synthesis requirements. Firstly, the peptide chain is divided into several peptide segments according to the sequence, and the yield of long and difficult peptide is increased.This method can also solve many problems in synthesis.

(2)Microwave synthesis

Although microwave radiation has been used since the late 1940s, microwave energy has gained new help in organic chemistry until 1986.Under the condition of microwave, the technology of microwave synthesis, which is used in the research of modern organic synthesis, makes use of its advantages of fast heating, homogeneity and selectivity, is called microwave synthesis.Microwave synthesis features fast heating speed.Because microwave can penetrate into the interior of matter, rather than rely on the heat conduction of matter itself, it only needs one tenth to one percent of the time of conventional method to complete the whole heating process.Otherwise a chemical reaction will take hours to days to complete.In the 20th century, many chemical technologies have been improved continuously. Microwave synthesizer has been designed as an important machine to provide low and high energy microwave energy, so that the temperature of reaction mixture can be controlled.The microwave energy used in peptide synthesis is a single frequency which provides the largest penetration depth sample, which is a very different breakthrough compared with the traditional kitchen microwave oven.In peptide synthesis, microwave radiation is used to complete long peptide sequences with high absorption and low racemization.The microwave irradiation not only catalyzes the growth of peptide chain by increasing temperature, but also aligns the polar backbone of the peptide by alternating electromagnetic radiation.Because of this phenomenon, microwave energy can prevent aggregation and thus increase the yield of the final peptide product.However, there is no clear evidence that microwave is better than simple heating. Some laboratories that produce peptides only use microwave as a simple method for rapid heating of peptide based resins.Heating to more than 50-55 degrees Celsius also prevents aggregation and acceleration of the coupling.

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