In today's era of rapid development in life sciences and biomedicine, peptide molecules are gradually moving from laboratory research to clinical applications.

As linear or cyclic molecules that connect multiple amino acid residues, peptides demonstrate unique advantages in regulating physiological activities, serving as drug carriers, and in vaccine development.

The peptide synthesis technology, as a key means for realizing these molecular designs and mass production, has become increasingly important.

Introduction to Peptides and Peptide Synthesis

Peptide is an organic molecule formed by the connection of amino acids through peptide bonds. It usually consists of 2 to 50 amino acid residues.

They are widely present in the body and are involved in various physiological activities such as hormone signal transduction, enzyme activity regulation, immune response, and antibacterial defense.

Peptide synthesis refers to the process of orderly connecting amino acid monomers in vitro to construct the target peptide molecule.

The goal of this process is to achieve precise structural control at the molecular level and to improve purity, stability and production efficiency through chemical methods.

Main Synthesis Methods and Their Development

Peptide synthesis technology can be broadly classified into the following three categories:

1.Solution-phase synthesis (Liquid-Phase Peptide Synthesis, LPPS)

This is an earlier application method, suitable for synthesizing short-chain or small-scale peptides. The reaction is flexible and the purity is high, but the operation steps are cumbersome and the extraction of intermediates is difficult.

2. Solid-Phase Peptide Synthesis (SPPS)

Proposed by American scientist Merrifield in 1963, it ushered in a new era of industrialization in peptide synthesis.The basic principle is to fix the first amino acid on the solid-phase resin, then gradually introduce other amino acids, and finally release the target peptide.

This method has a high degree of automation and is convenient for purification, and has become the current mainstream technology for custom peptide synthesis.

3. Enzymatic Synthesis and Biological Synthesis

In recent years, the synthesis of peptides using biocatalytic enzymes or genetic engineering techniques has also attracted attention.

It has the advantages of high selectivity and mild conditions, and is particularly suitable for medicinal peptides that are highly sensitive to configuration.

Key Challenges in Peptide Synthesis

Although the technology has become mature, it still faces various challenges in practical applications:

Low synthesis efficiency of long-chain peptides: An increase in chain length is likely to result in steric hindrance and folding errors;

Sequence-specific residue issue: Sequences rich in Pro, Cys, and Arg are less likely to be coupled;

High purity requirements: The purity of pharmaceutical peptides should be over 95%, which is quite challenging.

The cost control is quite challenging: the prices of amino acid monomers and reagents are high, and the processing cycle is long.

The Wide Application of Peptide Synthesis

Peptide drugs

Such substances as insulin, growth hormone, glucagon, and octreotide have all become commonly used drugs in clinical practice.

Vaccine development

Peptide vaccines have the advantages of high safety, clear targets and stable structure. In recent years, they have achieved remarkable success in the development of vaccines for COVID-19, HPV and HIV.

Antimicrobial peptides and immune regulation

Peptides can be used as substitutes for antibiotics, for the purposes of antibacterial, antiseptic and inflammation control.

Tumor targeted therapy

Peptides possess excellent targeting binding capabilities and can be utilized in drug delivery systems and cancer treatment.

Future Development Trends

The rise of fully automatic synthesis platforms: Modern instruments can now perform fully automated multi-peptide synthesis in one step.

Breakthrough in long-chain and modified peptide technology: By optimizing coupling reactions, end-group protection strategies, and click chemistry, more complex structures can be synthesized;

Application of green chemistry: Enzyme catalysis and aqueous reaction systems will reduce environmental impact;

Personalized customization: For precision medicine, the synthesis of customized therapeutic peptides is increasing.

Conclusion

Peptide synthesis is not only one of the core technologies in life science research, but also the fundamental platform that supports emerging industries such as modern biopharmaceuticals, high-end cosmetics, and intelligent materials.

With the dual impetus of technological innovation and market demand, peptide synthesis will continue to demonstrate its strong vitality in the future and move towards a new stage of more intelligent, green, and efficient development.

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