The History of Peptides: The Discovery and Subsequent History

What Are Peptides and What Is the History of Peptides?

Peptides are short chains of amino acids that are connected by peptide bonds. Once these chains are approximately fifty amino acids and above, they turn into proteins. Although shorter, the peptides have vital functions in biology and chemistry. They are hormones, cell-cell messengers, antibiotics and metabolic intermediates.

The history of the discovery of peptides dates back to over a century and involves organic chemistry, biochemistry, and molecular biology. Peptide research has been used by scientists to create complete industries, both pharmaceuticals and biotechnology. They also discovered the principles of protein synthesis and the molecular control systems of the body as they discovered how to make and modify peptides.

Early Chemical Indications in the 19th Century

During the nineteenth century, scientists were attempting to determine the chemical composition of proteins. They were aware that proteins were necessary to life but they did not know exactly what they were composed of and how they were organized.

Chemists like Jons Jakob Berzelius had observed that proteins had a high concentration of nitrogen and were not similar to fats and sugars. The improved analytical instruments enabled scientists to decompose proteins and determine their components. In 1820, Henri Braconnot warmed gelatin in sulfuric acid and found the simplest amino acid, glycine. In the following decades, other amino acids were discovered, such as leucine, tyrosine, and tryptophan.

The actual breakthrough was achieved when scientists came to understand that proteins were polymers composed of amino acids. They then enquired about the relationship between these units. Towards the end of the 19th century, Emil Fischer suggested that amino acids are fused with certain linkages that came to be referred to as peptide bonds. Short chains of amino acids were also produced in the laboratory by Fischer, which formed the basis of peptide chemistry.

The 20th Century Construction of Peptide Chemistry

Emil Fischer is considered by far the pioneer of peptide chemistry and the one who used the term peptide. As early as the 1900s, he had imagined that one day chemists would be able to construct entire proteins using simple building blocks. The development was slow and it took decades before this vision came into reality.

One of the greatest advances came in 1953, when Vincent du Vigneaud and his colleagues chemically synthesized oxytocin. This showed that a biologically active peptide could be produced completely by using chemicals. Other naturally occurring active peptides were discovered in the next years and subsequently produced or engineered in the laboratory.

The field of synthetic chemistry developed at a fast pace since the 1950s. One of the most important was the development of solid-phase peptide synthesis (SPPS) by Robert Bruce Merrifield in 1963. The initial amino acid is conjugated to an insoluble resin in this technique, and the chain is assembled by one amino acid at a time. The production of peptides was more reliable and much faster in SPPS as compared to liquid-phase techniques. It allowed routine production of peptides to develop drugs, vaccine research, diagnostics and basic science. Peptides have become indispensable today in medicine, biotechnology and even materials science.

The Rise of Modern Biochemistry (1920s–1930s): Insulin

Among the greatest medical discoveries that involved a peptide was the discovery of insulin in 1921 by Frederick Banting and Charles Best. The pancreas produced insulin which could be purified and used to treat diabetics. Prior to this, diabetes was normally terminal. Subsequently, it became manageable to a lot of patients. The breakthrough revealed that small protein-like molecules could be used to save lives.

During the next decades, chemists and biochemists tried to learn more about insulin and other peptide hormones. The methods of the era enabled scientists to determine the amino acids involved, but not the entire sequence in a convenient manner. There was gradual but gradual improvement.

In 1935, Adolf Butenandt and his colleagues extracted the peptide hormones oxytocin and vasopressin of the posterior pituitary. These mini peptides proved to be important in child birth, milk release and water balance. Their identification strengthened the notion that short peptide chains are the key regulators of essential physiological events.

A Mid-Century Turning Point

The 1950s marked a key decade. In 1955, Frederick Sanger established the entire amino acid sequence of insulin. He demonstrated the existence of two peptide chains in insulin joined together by disulfide bonds, and the existence of defined, ordered sequences in proteins. The publication made him win the 1958 Nobel Prize in Chemistry and essentially transformed how scientists approached proteins.

Meanwhile, the process of synthesis was also transformed. The introduction of solid-phase peptide synthesis by Merrifield in 1963 transformed the slow and fragile process into an automated and scalable process. Long peptides that were hitherto unattainable to assemble with confidence were now available. Merrifield was awarded the Nobel Prize in 1984 in appreciation of this revolutionary approach.

Peptides in Medicine and Research (1960s–1980s)

New synthesis methods provided new opportunities. The first peptide-based diagnostics and treatments emerged in the 1960s and 1970s. Gonadotropin-releasing hormone (GnRH) was first used in the 1970s and synthetic GnRH analogues were subsequently developed to treat infertility and some hormone-sensitive cancers.

Other peptide medicines were also developed. Onset and duration of action were fine-tuned by designing modified insulin analogues. Gramicidin and polymyxin are natural peptide antibiotics that were used against bacterial infections. Simultaneously, peptides were now routinely used in research laboratories as substrates of enzymes, small probes to investigate receptors, and as antigens to generate specific antibodies.

Molecular biology redefined the image during the same time. The identification of messenger RNA and the breaking of the genetic code in the 1960s demonstrated the way cells read genetic information and convert it into peptide and protein chains. Ribosomes were found to be the machineries of the cell that actually form peptide bonds. This connected peptide chemistry to genetics and molecular biology and bridged the gap between sequence, structure, and function.

The 1990s–Present: Peptides in Contemporary Science

Later in the 20th century and the 21st century, peptides gained even further importance in both basic and applied research. Better mass spectrometry enabled the detection and measurement of peptides in highly complicated biological samples. The method assisted in the creation of proteomics, the large-scale analysis of proteins and their peptide fragments. These instruments enabled researchers to map signalling pathways, disease markers and to gain a deeper insight into molecular processes within cells.

Peptides have also become a significant group of therapeutic drugs on the therapeutic side. By 2020s, over eighty peptide-based medicines were approved to be used in clinical practice, and numerous others were under development.

Examples include:

• insulin analogs in the management of diabetes
  
• Exenatide and liraglutide (GLP-1 receptor agonists) used in diabetes and obesity
  
• calcitonin in the treatment of bone disorders like osteoporosis
  
• peptide-based anticancer therapy, such as proteasome inhibitors like bortezomib
  

Compared to most small-molecule drugs, peptide drugs are commonly highly specific and relatively non-toxic. Nevertheless, they are limited. Most of them are readily degraded in the body and not absorbed well on oral intake. In order to overcome these, scientists have come up with modified peptides, peptide-drug conjugates, and improved delivery methods such as nanoparticle-based systems and other formulations that are aimed at protecting the peptide until it reaches its target.

Peptide engineering has also become very popular. Peptides containing non-natural amino acids, cyclic or stapled backbones, and other characteristics that render them more stable or more selective are now designed by scientists. Synthetic structures that mimic the shape and function of natural peptides are called peptidomimetics and have further extended these concepts and provided new avenues in drug discovery, materials science, and nanotechnology.

Quality Research-Grade Peptide Supply

With the growth of peptide work, there has been an increased demand of consistent and high-purity material to be used in the laboratory. Research organisations and laboratories depend on specialist suppliers that specialise in the manufacture of peptides and associated equipment only to be used in in-vitro and experimental studies.

Such suppliers are usually run with stringent quality systems, and their facilities are based on the current good manufacturing practice (cGMP) and are certified to standards such as ISO 9001. Peptide batches are periodically verified to be pure by methods such as high-performance liquid chromatography (HPLC) and current mass spectrometry (including MS-UPLC). The purity is usually over 98 percent and the products are kept at a controlled temperature to ensure stability.

A large number of catalogues currently sell a variety of standard peptides, custom sequences, combination packages, and basic lab supplies, and ship worldwide. The products should not be used or administered to human beings or other purposes other than research and analysis.

Closing Thoughts

The history of peptides has a history of over 100 years of research in chemistry, biology, and medicine. Since the listing of amino acids in the 19th century, with the initial attempts at synthesis by Emil Fischer, and the sequencing of insulin by Sanger and the introduction of solid-phase synthesis by Merrifield, each advance has been a new frontier.

The use of peptides has led to the discovery of protein structures, a variety of life-changing medicines, and technologies that are currently fundamental to biomedical studies. Now they are at the brink of knowledge that has been long-standing and new innovation, connecting fields and propelling therapeutics, biotechnology and nanoscience. The plain peptide bond between the amino acids is the one that keeps on joining not only the molecules, but also the whole science.