How are peptides made and how are peptides Synthesised?

How are peptides made and how are peptides Synthesised?

Peptide Synthesis: How Are Peptides Made?

Peptides are short chains of amino acids that play important roles in medicine, research, and skincare. But how do we actually make them?

There are two main ways:

  1. Biological Synthesis – This occurs naturally inside cells, where peptides and proteins are assembled by ribosomes.

  2. Chemical Synthesis – Scientists create synthetic peptides in a lab using solid phase peptide synthesis (SPPS) and other methods, which involve the formation of peptide bonds.

In this article, we’ll break down peptide synthesis, explore the different methods for producing peptides, and discuss how they’re used in modern science and medicine.

Understanding Peptide Synthesis

At its core, peptide synthesis is the process of linking amino acids in a specific peptide sequence to form a functional peptide chain. If you think of a peptide bond like a link in a chain, then the first amino acid of peptide coupling is the process of ensuring each link is properly connected.

In nature, our bodies synthesize peptides using complex biological machinery. In the lab, however, scientists carefully control every step using phase peptide synthesis (SPPS). The most important part of this process is peptide bond formation, which ensures that each amino acid producing a synthetic peptide is properly connected to first amino acid of the next.

Amino Acid Selection and Preparation

If peptide chains are like necklaces, then amino acids are the beads. But not all beads are the same—some are hydrophobic, others interact well with water, and some have amino groups that must be protected to prevent unwanted bond formation.

To avoid mistakes, scientists use side chain protecting groups to temporarily shield specific parts of the amino acids. Side chain protecting groups are especially important because they prevent unintended peptide coupling during synthesis of peptides.

Unnatural amino acids—those not found in nature—can also be included in peptide production to give synthetic peptides new properties, such as improved stability or resistance to degradation.

Carefully selecting and preparing amino acids ensures that the desired whole peptide sequence is made correctly.


Methods of Peptide Synthesis

There are three primary ways to synthesize peptides:

1. Ribosomal Peptide Synthesis (Natural Method)

This process occurs in living cells. Ribosomes follow instructions from messenger RNA (mRNA) to link one amino acid at a time, forming peptide chains of amino acids. The result is a synthesized peptide that may later fold into a functional protein or act as a peptide hormone like insulin or oxytocin.

2. Solid-Phase Peptide Synthesis (SPPS) (Lab Method)

Solid phase peptide synthesis (SPPS) is the most widely used method for producing peptides in a lab. It allows for stepwise, peptide synthesis and bond formation with better control and efficiency.

How it works:

  • The first amino acid is anchored to a solid resin.

  • Scientists add one amino acid at a time using coupling reagents to ensure proper amino acid coupling, which involves the formation of peptide bonds.

  • The growing peptide chain remains attached to the resin until the desired peptide is complete.

  • A strong acid, often trifluoroacetic acid, is used to remove the peptide from the resin.

Because SPPS simplifies peptide purification and allows for large-scale peptide production, it is the go-to method in peptide chemistry.

3. Liquid-Phase Peptide Synthesis (Older Method)

This older technique involves performing each amino acid coupling step in a liquid solution. While it allows for easier fragment condensation, it requires purification at every amino acid coupling step, making it time-consuming and inefficient compared to SPPS.

Despite its drawbacks, liquid-phase synthesis is still used for certain peptide drugs and industrial-scale peptide production.


Challenges in Peptide Synthesis (And Solutions, Including Disulfide Bond Formation)

Peptide synthesis protocols can be tricky, especially for longer peptides. Some common challenges include:

  • Disulfide bond formation – These bonds help stabilize peptide structures, but forming them correctly can be difficult.

  • Low yield and impurities – The longer the peptide sequence, the harder it is to ensure proper bond formation.

  • Steric hindrance – Some amino acids are bulky, making it harder to link them together.

Solutions:

To overcome these challenges, scientists use:

  • Microwave-assisted synthesis – Speeds up reactions and improves peptide yields.

  • Optimized peptide synthesis protocols – Helps prevent unwanted side reactions.

  • Trifluoroacetic acid cleavage – Ensures clean removal of the synthesized peptides from the solid support.


Peptide Purification and Quality Control

Once a synthetic peptide is made, it must be purified and tested before it can be used in medicine or research. Peptide purification removes impurities and ensures only the desired peptide remains.

Key Purification Techniques:

  • High-Performance Liquid Chromatography (HPLC) – Separates crude peptides from unwanted byproducts.

  • Mass Spectrometry (MS) – Confirms the peptide sequence by measuring molecular weight.

  • Nuclear Magnetic Resonance (NMR) – Verifies the structure and stability of the synthesized peptides.

Lyophilization (freeze-drying) is often used after peptide purification to preserve peptides for long-term storage.


Advanced Peptide Synthesis Techniques

Peptide science is always evolving. Some of the latest advancements include:

  • Incorporating unnatural amino acids to expand peptide functionality.

  • Fragment condensation to efficiently produce longer peptide chains.

  • Aqueous solutions for environmentally friendly peptide production.

New methods in organic chemistry and peptide chemistry continue to push the boundaries of what synthetic peptides and proteins can do.


Applications of Synthetic Peptides

  1. Medicine

Peptide drugs are really changing the way we treat many illnesses. I see insulin as a great example—it’s a peptide hormone that helps control blood sugar in people with diabetes. For many, it can be a lifesaver. Then there’s semaglutide, also known as Ozempic, which is a newer drug that not only helps control blood sugar but also assists with weight management. Researchers are also excited about peptides like BPC-157. They’re studying it because it might help speed up healing, reduce swelling, and repair damaged tissues. These discoveries could lead to better treatments in the future.

  1. Skincare

Peptides play an important role in modern skincare products. They help our skin by boosting collagen production, which makes skin repair itself and look smoother. Take GHK-Cu, for example. This peptide is known to help wounds heal and fight the signs of aging. Another one, Matrixyl, is a blend that works to boost collagen and reduce wrinkles. I love how these ingredients are added to creams and serums to help keep skin hydrated and fresh. They really help in reducing fine lines and keeping skin looking young.

  1. Scientific Research

In the world of science, synthetic peptides are powerful tools. Researchers use them to understand how proteins and other cell parts work together. By mimicking natural peptide hormones, scientists can test new drugs and get a better idea of how our cells respond. I find it fascinating that these peptides also help in developing vaccines. They can trigger a specific immune response without the need to use an entire germ, which makes them safer to work with. Overall, synthetic peptides let us dig deep into biology and help create better treatments and vaccines.

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Future of Peptide Synthesis

With continued advancements in peptide synthesis protocols, researchers are making the synthesis of peptides faster, cheaper, and more efficient than ever before. Exciting developments include:

  • Better large-scale peptide production methods.

  • New peptide-based drugs for cancer and autoimmune diseases.

  • Sustainable peptide synthesis using aqueous solutions.

As peptide chemistry advances, synthetic peptides will continue to drive innovation in medicine, research, and technology.


Final Thoughts

Whether made by ribosomal peptide synthesis in cells or through solid phase peptide synthesis (SPPS) in a lab, peptides are transforming healthcare, skincare, and biotechnology. The ability to synthesize peptides with precision and efficiency is opening new doors in peptide science—and the future looks promising.

Sources:

  1. • NCBI Bookshelf – Translation of mRNA (In: Cooper GM, The Cell: A Molecular Approach, 2nd ed. 2000):
    https://www.ncbi.nlm.nih.gov/books/NBK21054/

    • Wikipedia – Overview of Solid-Phase Peptide Synthesis:
    https://en.wikipedia.org/wiki/Solid-phase_peptide_synthesis

    • Wikipedia – General Peptide Synthesis Overview:
    https://en.wikipedia.org/wiki/Peptide_synthesis

    • Crochetastic Boutique – Understanding Peptides (For both peptide drugs and skincare benefits):
    https://www.crochetasticboutique.com/understanding-peptides