The solid-phase synthesis of peptides is currently the most convenient and commonly used method for peptide synthesis. The first amino acid at the C-terminus of the peptide is coupled to an activated carrier (such as polystyrene). Resin can serve as both a C-terminal protective group and rapidly separate the growing peptide product from the reaction mixture formed during the synthesis process.



What Should You Pay Attention to When Long Peptide Synthesis?

In protein chemical synthesis research, solid-phase synthesis method is the most commonly used and simplest synthesis method. This method is also effective in synthesizing long-chain peptides, but as the peptide chain lengthens, the reaction gradually becomes more difficult (such as greater than 150 amino acids), and some target peptides with missing residues are produced. These peptide chains with missing residues are also the main impurities generated during the synthesis of long peptides.



Therefore, the main difficulty we need to overcome in the synthesis of long peptides is to explore better reaction conditions and methods, so as to make the amino acid condensation reaction more complete and thorough. At the same time, shorten the reaction time, because the longer the reaction time, the more uncontrollable side reactions there will be, and the more complex the by-products will be. These by-products are also important components of the impurities produced by the entire reaction.

In order to solve the many problems in the synthesis of long peptides, Omizzur Biotech has adopted a series of effective measures and methods:

(1) Microwave Synthesis Method: 

For some amino acids that are difficult to condense during the synthesis process, we use microwave method for synthesis. This method has significant effects, greatly shortens the reaction time, and reduces the production of two main by-products.

Omizzur's microwave technology support: It is a peptide synthesis method under microwave administration.

Greatly improve reaction speed. Shorten the synthesis cycle of peptides and improve synthesis efficiency.

Under microwave radiation, the synthesis of disulfide bonds was carried out, which shortened the reaction time and improved the purity and yield of the product.

Based on microwave technology support, Omiizur Biotech has launched a rapid peptide synthesis business, with delivery within 4 days faster than 10aa

(2) Fragment Synthesis Method: 

When certain peptides are difficult to synthesize and purify using conventional synthesis methods, we also use a method of condensing several amino acids in a certain segment of the peptide as a whole onto the peptide chain. This method can also solve many problems in synthesis.

In the requirements of peptide synthesis in reality, it is difficult to synthesize peptides with more than 40 amino acids. Omizzur Biology uses fragment condensation method to synthesize longer peptide fragments, which are divided into several parts and synthesized separately. Then, through certain methods, the synthesized shorter peptide fragments are connected to form complete peptide fragments.

The characteristic of using fragment synthesis method to synthesize long peptides is significantly higher in synthesis efficiency and purity than direct method. Omitzur organisms typically synthesize lengths of 4-50aa. A length of up to 150aa can be synthesized through fragment condensation technology.

(3) Hydrazide Synthesis Method: 

The method of synthesizing peptides by hydrazine method is a chemical selective reaction between the N-terminal Cys peptide and the C-terminal peptide hydrazide synthesized by solid-phase synthesis to form amide bonds and achieve peptide linkage. This method divides the entire peptide chain into multiple sequences based on the position of Cys in the peptide chain, and synthesizes them separately. Finally, the target peptide is obtained through liquid-phase condensation reaction. 

This method not only greatly shortens the synthesis time of long peptides, but also significantly improves the purity of the final product, making it widely applicable for the synthesis of long-chain peptides containing Cys.

We often have clients inquiring about the synthesis of ultra long peptides, such as those with lengths ranging from 100 to 200 amino acids. In fact, 200 amino acids already belong to the category of proteins. The successful synthesis of a protein containing 160 amino acids proves that our synthesis technology is fully capable of synthesizing long peptides on existing technology platforms.

Our technology platform usually synthesizes peptides of less than 60 amino acids (peptides of this length are most commonly used by researchers), but through our modifications to peptide linking technology and synthesis methods for long peptides, we are now able to successfully synthesize peptides of protein length.



Purification of Long Peptides

The unique nature of long peptides inevitably leads to complex crude peptide components, making HPLC purification of long peptides a challenge; By drawing on a wealth of experience in the purification process of amyloid series peptides and successfully applying it to the purification of long peptides, we have significantly improved the success rate of our long peptide purification through the use of new equipment, mixed purification systems, repeated separation, and other empirical methods.

Advantages of Chemically Synthesizing Peptides and Proteins

Obtaining peptides or proteins of up to 100 to 200 amino acids through chemical synthesis is faster and cheaper compared to other methods. Chemical synthesis of proteins is carried out in the order of amino acids, without errors or variations.

Chemical synthesis can also incorporate modifications that cannot be achieved by other methods, such as replacing conventional amino acids with D-type amino acids, increasing phosphorylation or methylation at a certain site. Chemical synthesis does not require additional tags for purifying proteins, such as 6HIS or FLAG.

In terms of protein expression methods, gene synthesis, plasmid construction, protein expression, and purification occupy the vast majority of time and cost. Therefore, the chemical synthesis method of long peptides is a worthwhile approach for scientific research.

Omizzur Long Peptide Synthesis Case

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