As the name suggests, peptide synthesis is the sequence of creating peptides, compounds made up of several amino acids connected by amide bonds, also called peptide bonds. They are chemically synthesized through the condensation reaction of one amino acid’s carboxyl group to another amino group.
To avoid any kind of undesirable side reactions with plenty of amino acid side chains, protecting group strategies are typically needed. Chemical peptide synthesis is most generally initiated at the peptide’s carboxyl end (C-terminus) and progresses to the amino terminus or N-terminus. Protein biosynthesis or long peptides usually occurs in the opposite direction in living organisms.
What are some facts that you should know about peptide synthesis?
The process of peptide synthesis moves through different stages. There is a lot to learn in this regard. Here are some facts related to peptide synthesis, which will charge your grey cells:
Fischer and Fourneau announced the first peptide synthesis and the invention of the word “peptide” (Fischer and Fourneau, 1901). Bergmann and Zervas invented the carbobenzoxy (Cbz) group as the first reversible N-protecting group for peptide synthesis (Bergmann and Zervas, 1932).
DuVigneaud successfully used early “classical” methods to create an oxytocin-like peptide (Vigneaud et al., 1953). Classical, or solution-phase, methods for peptide synthesis have a long and illustrious history. Solution synthesis is still beneficial in large-scale production and advanced laboratory applications.
Bruce Merrifield invented solid-phase peptide synthesis, for which he received the Nobel Prize. He was able to drive reactions to completion with massive amounts of reagents. He cleaved the peptide from the support in relatively pure form by anchoring the C-terminal amino acid of the peptide to insoluble resin support.
Racemization is converting an optically active compound into a racemic form through heat or chemical reaction. One of the most damaging side effects of chemical peptide synthesis is amino acid racemization. It is well established that the biological activities of peptide/protein molecules are directly related to their dimensional atomic alignments. In contrast, inversion of the configuration at specific peptide chiral centers can cause local spatial rearrangement of the critical functional groups. Custom peptide synthesis service provides a wide range of synthesis platforms, purity standards, upgrades, and formats to address several research needs.
Furthermore, racemization of a single amino acid in a peptide chain may substantially affect the overall conformation of the affected molecule. Both of these factors can significantly influence the biological activities of the peptide molecules in question.
3. Peptide Deprotection
Since amino acids have several reactive groups, peptide synthesis is carefully done to prevent side reactions to shorten and branch the peptide chain. Chemical groups bind with the amino acid reactive groups and then block, or shield, the functional group from entirely nonspecific reactions to facilitate peptide formation with minimal side reactions.
Individual amino acids used here to synthesize peptides react with the protecting groups before synthesis, and unique protecting groups are then removed from this newly added amino acid (a unique step known as deprotection). This occurs right after coupling that enables the following amino acid to bind to the expanding peptide chain in a proper orientation. When the peptide synthesis is finished, all the remaining protecting groups separate from the nascent peptides.
A very crucial step takes place after deprotection, called cleavage. When a resin gets exposed to a cleavage cocktail, it undergoes several competitive reactions. The target peptide can be irreversibly changed or destroyed if the correct reagents and reaction conditions are not used during the cleavage step.
4. Peptide Vaccines
The recent rise in peptide vaccine research indicates that it will play an essential role in next-generation vaccine systems. Vaccines are critical in protecting individuals as we all as community health by minimizing infectious disorders, injury, and deaths and preventing and eradicating long-term disease.
The development of high-purity subunit vaccines containing a small portion of the pathogen required to elicit an immune response serves as the foundation for new vaccine technologies. Polysaccharides and proteins, or their peptide fragments, go into the making of subunit vaccines. Synthetic peptide vaccines are made up of 20–30 amino acids that contain the primary epitope of a corresponding antigen against a variety of diseases.
There is no distinction between cancer and allergies in diseases targeted by peptide vaccines. Due to the benefits of peptide vaccines, peptides are now preferred in vaccine technology. Although several peptide vaccine trials are ongoing, no peptide vaccine for human use has been authorized. Peptide vaccines are critical in producing effective, safe, inexpensive, and easy-to-produce vaccines by the advantages and the development of new adjuvants.
5. Making Peptides At Large Scale
The peptide ingredient market is expanding, and drug developers request that custom manufacturers create the next generation of peptide drug candidates. Although these peptides are longer and more complex than previous generations, technological advances and economies of scale have made processing more efficient and cost-effective. Contract manufacturers are assisting in transforming peptides into affordable and efficient medicines by using various synthetic and recombinant techniques.
Stable peptides can now be generated, and the therapeutic peptide industry is expanding into new disease areas. There are approximately 60 peptide drugs on the market, with nearly ten times the preclinical and clinical development number.
While peptide manufacturers are divided into chemical synthesis and recombinant production—most observers believe this divide would fade. However, rather than one solution supplanting another, they are more likely to compliment or even merge. The distinction between peptides and min proteins would also vanish due to the chemical synthesis of much larger proteins and increased recombinant production of shorter peptides.
The Bottom Line
With available materials and techniques, synthetic chemistry will solve the problems like mass production and availability. The peptides developed for various uses, such as medications, vaccines, and therapeutics, will cure incurable diseases such as certain epidemic diseases and certain cancer forms. The facts mentioned above become the basis of peptide science, which can be developed academically within the next decade. However, there are specific facets of peptide synthesis that one must know.