Advances in biotechnology have led to multiple strides in protein synthesis, including commercial peptide production. Peptides are structural bonds that facilitate the linkage between amino acids to form proteins.
Recombinant peptide production is at the heart of multiple pharmaceutical applications that help improve the quality of life for many individuals. For instance, the process facilitates the linkage between amino acids that would otherwise not bond, leading to the synthesis of unique proteins.
The process begins with custom antibody, a natural process, although technological advancements facilitate chemical synthesis. Below is everything you need to know about recombinant peptide production.
It Begins With Solid-Phase Peptide Synthesis (SPPS)
Artificial peptide production was a labor-intensive process until solid-phase peptide synthesis (SPPS) came to be. According to one literature review, the technique is a successor to previous or “classical” strategies used to synthesize peptides.
The primary difference between SPPS and classical methods is that while the latter utilizes liquids to form the polypeptides, SPPS utilizes polymeric support. Solid polymeric support is a substrate or surface with a high adhesion capacity for resin or organic compounds, and examples include glass, ceramics, and specific metal surfaces.
Consequently, the first step in SPPS is adhering the resin (can be purely organic or synthetic) to the available polymeric support apparatus. SPPS entails successive chain reactions to form amide (peptide) bonds between amino acids to form a peptide chain.
Amide bonds typically feature one carboxyl group (C terminus) attached to an amino acid (N terminus). So, the chain reaction proceeds unidirectionally from the C terminus to the N terminus.
Another significant factor in SPPS is that it utilizes a protection strategy to keep the chain reaction linear by preventing side reactions that lead to undesirable bond formation. The protective strategy entails using amino-protecting groups to keep each peptide inert until it is its turn to bind with the carboxyl group.
SPPS utilizes the 9-fluorenylmethoxycarbonyl (Fmoc) and the tert-butyloxycarbonyl (Boc) protective groups. The said protective groups are ideal because they allow for simple cleavage mechanisms using an aqueous solution to deprotect protected amino acids, facilitating the reaction. SPPS utilizes selective deprotection to ensure that only one amino acid gets cleaved at a time, preventing side reactions.
Although classical peptide synthesis techniques also utilize protection strategies using different protection groups, SPPS has a bonus step. The solid-phase peptide synthesis technique includes capping to prevent the ends of the newly-formed peptide chain from reacting. SPPD has many advantages, including speed, efficiency, fewer purification steps, and you only require a small amount of resin to form the peptide you desire.
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Peptide Synthesis Allows The Formation Of Peptides Challenging To Express In Bacteria
Although peptides play a significant role in biochemistry, some peptides are much more challenging to produce than others. However, SPPS overcomes the challenges that in-vitro peptide synthesis using organisms like bacteria present.
A good example is the synthesis of peptides that bear toxicity towards the host cell, such as antibacterial peptides. Therefore, SPPS presents an efficient technique to synthesize diverse peptides, including amide bonds that do not typically exist in nature.
Peptide Synthesis Facilitates Protein Backbone Modification
Peptides are short-chain groups of two to twenty amino acid molecules, and multiple peptides form a protein strand. The amide links between the group of peptides in a protein strand make up the backbone of a protein molecule. A protein molecule’s backbone also makes up the molecule’s tertiary structure.
Biotechnological advances in protein synthesis include protein backbone engineering, which allows for post-translational protein modification. Protein backbone engineering utilizes peptide synthesis to insert unique peptides (ester substitution) into the protein backbone, creating proteins with enhanced functions.
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Peptide Synthesis is At The Heart of Cancer Therapy Research
According to 2021 cancer prevalence statistics, US health facilities reported approximately 1.9 million new cancer diagnoses during the year. Moreover, they also recorded 608,570 thousand cancer-related deaths within the year.
Given the ravaging effects that cancer has on patients and society as a whole, researchers are constantly working on effective therapies to help counter the ravenous disease. One line of research that holds immense promise is protein synthesis, including peptide synthesis.
An example is peptide radiopharmaceutical therapy, which uses radiopharmaceutical peptides to target and bind pretentiously to cancerous cells. Clinical trials using radiopharmaceutical peptides report that the treatment presents fewer side effects among patients.
Peptide Synthesis Is Key To Drug Development
Besides cancer treatment, peptide synthesis is also a critical process in drug design and development. Ideally, drugs work by binding to targeted proteins, initiating their pharmacokinetic activity.
According to one research review on biopharmaceutical drug development, peptide synthesis increases the binding capacity for synthetic peptides. Enhanced binding increases the peptide drug’s bioavailability.
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Peptide Synthesis Enhances Antibody Creation
Peptide synthesis is also a significant process in vaccine development. Unlike conventional vaccines that utilize antigens to trigger an immune response, peptide synthesis utilizes immunogenicity.
Immunogenicity utilizes natural cells as antigens to trigger a natural immune response. According to one literature review, peptide vaccines use synthesized peptides less likely to cause allergies to trigger the immune response. Moreover, the peptides also allow for epitope mapping or an experimental process that helps identify the ideal binding site for the vaccine.
Peptide synthesis is the backbone of recombinant protein production, aimed to improve various preventive and curative therapies. Therefore, understanding the technique is the first step towards understanding its relevance in pharmaceutical research.