In the age of modern technology and medicines, researchers have come a long way. Back when peptides were still a subject of unsuccessful trials, not many types of equipment were present to conduct tests on therapeutic peptides. However, in the 21st century, many aspects of it have transformed. Now, peptide therapeutics play a notable role in medical solutions since the emergence of insulin therapy. In addition, the United States has approved more than sixty peptide-based drugs. Furthermore, peptide drug discovery has manifolded beyond its standard focus.
Modern-day researchers and scientists adhere to peptides as well-tolerated, relatively safe, productive, and highly selective. Consequently, there is an expanding interest in pharmaceutical R and D, with over 140 peptide therapeutics being evaluated in clinical trials currently. Moving on, let’s discuss some of the factors that have made the custom peptide synthesis process seamless and in-demand.
The Emerging Therapeutic Applications of Peptides
Peptides tend to play a significant role as signing molecules when it comes to human metabolism regulation. Researchers have tested and observed the efficacy of utilizing such molecules as potential medical agents for several years. Besides, when the first peptide experienced isolation through exogenous applications, that’s when scientists and pharmaceutical organizations realized its potential. Back in the 1920s, some of the chemists from the Toronto University discovered the first isolated therapeutic peptide. They could utilize and test purified pancreatic extracts comprising insulin to treat diabetes. Such exogenous insulin could effortlessly imitate endogenous molecules and, consequently, become one of the replacement therapies.
Insulin with ACTH or adrenocorticotropic hormone was further purified through pituitary glands. Not only was it considered a quintessential life-saving therapeutic in the initial half of the twentieth century, but it also became relatively more effective in the mid-1950s. Post these terms, industries, and researchers finally understood the actual potential of such biopharmaceuticals.
Initial Steps Of Peptide Synthesis
As already discussed, the US, along with Japan and most of Europe, has approved more than sixty peptides. However, researchers have incorporated close to one-fifty peptides under vigorous testing, with an average of 15-20 new ones making it every year since 2010. Compared to protein-specific medicinal agents, peptides consist of more than ten percent of the worldwide pharmaceutical industry. Moreover, it is essential to know that such advancement was only viable due to the improvement and development of the chemical peptide synthesis process.
Bruce Merrifield, considered the founder of modern peptide synthesis, was the one who revolutionized such a method by forming a solid-phase system in the early 1960s. But, before he discovered such a method, synthesizing peptides was no less than a complex and time-consuming process with adverse limitations because of their intrinsic instability in specific solutions. Bruce Merrifield transformed the situation by anchoring its chains to an insoluble and inert polymer.
Such innovation later enabled the complete systematization of the whole process and achieved the chemical rounds of synthesis of significant peptides. This was one of the accomplishments that were practically impossible to regenerate peptides utilizing traditional techniques. His achievement landed him a Nobel award in Chemistry, changing the field of peptides under various applications.
Peptide Synthesis Technologies – Solid-Phase Development and Saturation
Researchers and bioscience laboratories are aware of peptides that can be assembled through a step-specific process from the C to N terminus utilizing Nα-protected amino acids. It is essential to know that these peptide groups were pivotal in minimizing side reactions that could reduce a peptide’s intended size. Moreover, it could also lead to branching the peptide chain.
One of the first reversible Nα-protecting groups under peptide synthesis was expressed by a couple of chemists, Leonidas Zervas and Max Bergman, in 1932. Furthermore, while the Boc chemistry was reshaped and tuned by Merrifield and his team from the 60s to the 80s, such a method took shape into a mature technology. However, because of the adverse acidic issues, its utilization became relatively restricted than before. This took place after Grace Han and Louis Carpino presented descriptions of base-labile Fmoc Nα-protecting groups in 1970.
Fmoc chemistry also offered distinctive complexities. But, the replacement of robust mild base acids led to an increase in the peptide synthesis yield rich in Trp. These residues were referred to as immeasurable suffer modifications within the indole ring because of acid-catalyzed side reactions. When researchers adhered to these testings, they faced poor yields of peptide synthesis for Trp-specific peptides like an antibiotic peptide – gramicidin A.
Meanwhile, the Fmoc approach has successfully replaced Boc chemistry to promote solid-phase commercial peptide synthesis. Nonetheless, many laboratories utilize Boc chemistry to synthesize base-sensitive or complex peptides. Independently of the groups concerning Nα-protectors, the solid-phase method has preserved its original steps and principle. This occurs when you couple the protected amino acid residues with peptide extension and proceed with a series of coupling cycles and deprotection.
Uses of Peptides in Biopharmaceutical Development and Therapy
Because of inexpensive production and fully optimized peptides, biomolecules have established numerous uses for a vast application range:
- Vaccines: Modern problems require modern solutions. That is why many companies have started testing peptides to produce peptide-specific vaccines, replacing traditional ones.
- Immunogens: Peptides utilized alone or in combination with a carrier protein may lead to highly specific immunogens. Such a process produces only a handful of peptide antibodies.
- Binders: People can utilize peptides as binders to test antibody affinities or fragments against limited antigen epitopes for in-vitro procedures like the phage display.
- Radionuclide therapy: Researchers can also use radiolabeled peptides as vectors to treat terminal patients with metastatic tumors.
- Medical imaging: Specific peptides can be administered or radiolabeled to imaging targets that are challenging to reach.
The Bottom Line
The use of solid-phase peptide movements has not only emerged recently, but it has also shown potential in the discovery of some of the most effective therapeutic peptides. This has further allowed these molecules to discover new drugs and diagnostic operations. Despite some recent advances in recombinant processes, such a chemical method has become a prevalent way to synthesize peptide expressions.