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All You Need To Know About Custom Peptide Synthesis

Peptide synthesis entails artificially assembling two or more amino acids into peptide chains by triggering reactions that form covalent bonds between the amino acid molecules. It is the backbone of recombinant technology and utilizes cell-free systems to produce naturally occurring and novel peptides and proteins on an industrial scale. 

The process has diverse research and real-life applications in multiple areas, including drug development, preventative therapy, and therapeutics. Moreover, the rising demand for custom peptides makes artificial peptide production affordable. However, understanding the process guides you in outsourcing professional services, so learn about novel peptide synthesis below. 

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You Can Select Desirable Peptides From A Custom Peptide Library 


The existence of peptide libraries has simplified unique peptide production significantly. A peptide library is a collection of all possible cloned systemic peptide combinations, and one study shows that peptide research has yielded over 7000 possible peptide combinations.  Moreover, custom displays novel or custom peptides that do not exist naturally. 

Therefore, having access to a comprehensive peptide library can help you identify the resin you need to synthesize the desired peptide. Nonetheless, artificial and custom peptide synthesis are a time-involving, expensive, and delicate process, even for naturally-occurring peptides.  

Attempting to synthesize desirable peptides without professional help is ill-advised because professional services utilize experts with ample experience to troubleshoot undesirable incidences. Such services prioritize maximum yield and peptide quality and have the workforce and technical equipment to support scalability. 

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Custom Peptide Synthesis Is Cell-free 


Initially, the primary process utilized during peptide synthesis was cell-based or heterologous expression systems. Heterologous expression is an in vitro peptide and protein production process that entails inserting a desirable complementary DNA (cDNA) or a cRNA into host cells or expression systems.  

The host cell replicates a cell’s environment and uses the inserted DNA to express gene products, including the desired protein peptide. Examples of heterologous expression systems include select bacteria, fungi, insect, and mammalian cells. 

However, cell-based expression systems have multiple disadvantages. First, they take significantly longer than chemical peptide synthesis, present difficulty in expressing some peptides, endotoxin accumulation in the cell, and a more costly expression process. 

On the other hand, cell-free or chemical peptide synthesis entails using either the solid-phase peptide synthesis technique (SPPS) or solution phase/ liquid-phase peptide synthesis. SPPS entails attaching a biological compound sample with the desirable peptide content onto a polymeric support. 

Once the biological compound or resin is in place, a polymer reagent triggers a chain/ condensation reaction, forming covalent bonds. The covalent bonds form as an aqueous acid solution deprotects subsequent amino acid molecules preventing side reactions. 

Unlike heterologous expression, SPPS facilitates the addition of target amino acids during the chain reaction, forming custom peptides. Therefore, another advantage of custom peptide synthesis is peptide modification. 

As stated above, solution-based peptide synthesis is also an option when synthesizing chemically-produced custom peptides. The technique is ideal for producing short peptide sequences and scalability. However, SPPS is the industry standard for peptide synthesis because it is less labor-intensive, faster, and can produce long peptide chains. 


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Custom Peptide Synthesis Can Improve Peptide Stability and Bioavailability 


As stated above, SPPS allows for the modification of a peptide during the chain reaction to yield peptides with desirable characteristics. Such modifications can help improve peptide stability. 

In vivo or unmodified proteins have poor metabolic stability, leaving them vulnerable to proteolytic degradation, biotransformation, and immunogenicity. Proteolytic degradation occurs when enzymes break peptide bonds into constituent amino acids. On the other hand, biotransformation occurs when a compound undergoes alteration after administration into an organism, lowering its bioavailability. 

However, custom peptide synthesis allows for post-translational chemical modification to make the custom peptide more stable by enhancing proteolytic resistance. One popular method applied to enhance synthetically-produced peptide stability is covalent conjugation which blocks a peptide’s active sites, preventing non-targeted reactions like immunogenicity. 

Second, researchers may also utilize carboxyl-terminal (c-terminal) amidation during the chain reaction to reduce the terminal’s reactivity. Such chemical processes are game-changing custom peptide applications, particularly in peptide drug development. 

Custom Peptide Synthesis Supports Varying Peptide Lengths And Purity Levels 


According to one literature review, long peptides are arguably the most difficult to successfully express via heterologous expression, often leading to unacceptable yields. Moreover, long peptides expressed via heterologous systems complicate the purification process. However, custom peptide synthesis via artificial recombination allows the production of short-chain and long-chain peptides within weeks. 

Second, artificial peptide recombination demands less purification effort because separating the target peptide from cell debris is unnecessary. However, you can order custom peptides in different purity levels, from 50% pure to 99.9% pure. Various service providers offer different purity guidelines. 


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Peptide Analysis and Stability Testing Is Vital 


Custom peptide production yields a higher volume of target peptides, but analysis is essential to confirm peptide volume. Besides peptide volume, analytical tests like high-performance liquid chromatography (HPLC) also test target peptide quality to ensure it functions as it should. Moreover, peptide stability tests are also vital for their performance, so ensure your custom peptide service provider includes analysis and stability testing in the final price quotation. 



Custom peptide synthesis is a pioneering field, changing the landscapes in various industries one unique peptide at a time. However, understanding the technicalities involved in the process helps you choose the ideal production method for your project. 

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