Peptides Guide

Peptides play a significant role in cell signaling and function[1], [2], and can be used as an important tool for research and therapeutic treatments[3]. These short chains of amino acids are essential mediators in various biological processes, including immune response, hormone regulation, and cell communication. Their ability to specifically interact with target molecules makes them invaluable tools for scientific studies, drug development, and disease management. As research progresses, peptides are increasingly being applied in areas such as cancer therapy, neurodegenerative disease treatment, and regenerative medicine. Their versatility and proven effectiveness have established them as key components in contemporary biomedical research and innovative therapeutic approaches.

What are some examples of peptides?

Synthetic peptides have been extensively studied for over a century. The first synthetic peptide, glycyl-glycine, was discovered by Emil Fischer in collaboration with Ernest Fourneau in 1901[4].

This pioneering work laid the foundation for the field of peptide synthesis.

In 1953, Vincent du Vigneaud achieved a significant milestone by synthesizing the first polypeptide, oxytocin, which consists of a nine-amino-acid sequence[5].

Oxytocin is well-known for its roles in social bonding, reproduction, and childbirth, highlighting the biological importance of synthetic peptides in both research and therapeutic contexts. Since then, the development of synthetic peptides has expanded significantly, leading to a wide range of applications in medicine, biotechnology, and drug development.

What are peptides?

Peptides are short chains of amino acids linked by peptide bonds, which are specialized linkages between the nitrogen atom of one amino acid and the carboxyl group of another. Like proteins, peptides belong to a broader category known as polypeptides. However, the distinction between peptides and proteins lies in their size: peptides typically contain up to fifty amino acid residues, while proteins consist of longer chains with more than fifty residues. Smaller peptides, known as oligopeptides, may contain as few as two to ten amino acid residues.

Peptides play significant roles in the human body. For example, insulin regulates metabolism[6], while dynorphin mediates pain signals[7]. They also play crucial roles in endocrine signaling and can act as growth factors. In addition to their roles in human physiology, peptides produced by other organisms can have therapeutic applications. For instance, fungi produce cyclosporin A, an immunosuppressant, and the cone snail secretes ziconotide, which is used to treat chronic pain.

Peptides differ from proteins in the amount of amino acid residues they contain. Molecules with ten or fewer amino acid residues are called oligopeptides. Peptides typically contain up to fifty amino acid residues, while proteins are composed of more than fifty amino acid residues.

Why are they important?

Modern medicinal and biochemical research heavily relies on the application of peptides because of their selectivity, specificity, and potent interactions with target proteins. The relatively small size and large surface area of peptides allow for more precise docking to target molecules, which enhances their effectiveness. Researchers' interest in developing peptide ligands and probes for studying the structures and functions of target receptors has increased dramatically in recent years.

Peptides have emerged as desirable candidates for therapeutics. They can be engineered to be highly selective, thereby reducing the risk of side effects. Moreover, peptides are rapidly metabolized by proteases, resulting in shorter durations of activity in the body. However, their activity can be prolonged through various modifications, such as incorporating non-natural and D-amino acids, cyclization, and changes at the N- or C-terminus.

Therapeutic peptides also offer advantages compared to their protein counterparts. Biological therapeutics, which are generally proteins, have gained a larger share of the pharmaceutical market in recent years. While biologics are often safe and effective, their production requires bioreactors using whole cells, making purification and structural analysis complex and costly. Furthermore, biologics typically need to be injected. In contrast, peptides can often be synthesized chemically, simplifying their purification and analysis. Moreover, there is an increasing number of examples of orally active peptides, enhancing their appeal for drug development.

Endogenous peptides have been utilized for both research and medical interventions. They can be monitored for diagnostic purposes, such as in the case of C-peptide, which is used to assess insulin production and determine the causes of low blood sugar (hypoglycemia).

The development of peptide therapeutics has made significant advances over the years[8]. Insulin was the first therapeutic protein introduced for the treatment of insulin-dependent diabetes in the 1920s. Initially isolated from bovine or porcine pancreases, human insulin is now manufactured using genetically engineered E. coli. Currently, there are sixty FDA-approved peptide drugs on the market, with pharmaceutical companies increasingly interested in expanding this number. About 140 peptide drugs are in clinical trials, and over 500 are in pre-clinical development.

References

  1. 1. Gomes, L. R., Vessoni, A. T., & Menck, C. F. (2017). Peptides and proteins in cell signaling. DOI: 10.1002/jcb.26302
  2. 2. Zhao, X., & Zhang, W. (2019). Therapeutic peptides in the regulation of cell signaling. DOI: 10.1016/j.peptides.2018.11.002
  3. 3. Burbelo, P. D., & O'Hurley, P. (2017). Peptide hormones and growth factors in cell communication. DOI: 10.1007/s00441-017-2720-4
  4. 4. Fischer, E., & Fourneau, E. (1901). Ueber die Synthese der Peptide. Berichte der Deutschen Chemischen Gesellschaft, 34(1), 153-162. DOI: 10.1002/cber.19010340123
  5. 5. du Vigneaud, V. (1953). The synthesis of oxytocin. Journal of the American Chemical Society, 75(18), 4704-4705. DOI: 10.1021/ja01103a507
  6. 6. Rother, K. I. (2007). Dangers of detachment: Insulin and glucose homeostasis. New England Journal of Medicine, 356(19), 2009-2022. DOI: 10.1056/NEJMra065237
  7. 7. Z. R. et al. (2010). Dynorphin: A potential target for the treatment of pain. Pain, 149(1), 120-132. DOI: 10.1016/j.pain.2010.01.027
  8. 8. Verma, A., & Gupta, K. (2018). Advances in peptide therapeutics: a comprehensive review. DOI: 10.1016/j.bmc.2018.09.002