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Peptide Synthesis: What You Need To Know

Peptide Synthesis: What You Need To Know

More and more, we’re witnessing groups that would historically take up only possibly biology/biochemistry or traditional organic chemistry include peptides into their research programs.

Though this is perfect for bringing diversity in the peptide space and expanding the application diversity and scope in the peptide space, bringing synthesis into space can be an overwhelming task.

For most peptide chemists, the procedure of synthesizing, then cleansing, and ultimately drying down their peptide (or peptide workflow) is a crucial process that they must finish before an actual experiment can begin.

Maybe you’re learning about peptide synthesis for the first time. Or, you’d like to experiment on it but know very little about the process. Then, keep reading this post for more details. 

What is Peptide Synthesis?

Peptide synthesis is the creation of a peptide between several amino acids. While there’s no solid definition of a peptide, it usually points to flexible (tiny secondary structures) chains of at least 30-50 amino acids.

The capacity to create peptide bonds to connect amino acids is more than 100 years old, although scientists didn’t synthesize the first peptides, including insulin and oxytocin, for another 50-60 years.

This demonstrates the difficulty of chemically synthesizing amino acids’ chains. Nevertheless, in the last 50 years, progress in protein synthesis techniques and chemistry has grown to the extent that peptide synthesis is currently a typical drug and item development approach and high-throughput biological investigation.

Obstacles to Overcome to Synthesize a Peptide from Amino Acids

There are several hurdles you should defeat when amalgamating a peptide from its component amino acids.

One of them is analytical in character and is demonstrated by the dipeptide Ala-Gly as a suggested target. 

Should we disregard the chemistry entailed, a combination of equivalent molar amounts of glycine and alanine would give rise to four various dipeptides. They are:

  • Gly-Ala
  • Ala-Ala
  • Ala-Gly
  • Gly-Gly

In peptides, the amount of likely items from these two amino acids elevates to eight. Thus, you must practice some selectivity if you want to keep off complex combinations.

The second challenge comes from the fact that carboxylic acids and one or 2-amines don’t create amide links on connecting but will generally respond by proton shift to provide salts (the intermolecular equal of zwitterion development).

From the outlook of an organic chemist, peptide amalgamation needs selective acylation of an unrestricted amine. 

To achieve the desired amide bond development, we must first put off all irrelevant amine functions so they don’t contend for the acylation reagent.

Afterward, we must selectively switch on the appointed carboxyl function to acylate the single remaining unrestricted amine. Luckily, enzymatic responses that allow us to achieve these selections are widely known.

First of all, amide formation substantially lowers the nucleophilicity and basicity of amines. As an outcome, amino acid acylation by treatment with anhydrides or acyl chlorides at pH > 10 serves to shield their amino acids from an additional reaction.

Second, acyl halide or anhydride-like activation of a particular carboxyl reactant must happen as a preliminary to a peptide (amide) link creation. 

This is achievable as long as contending responses involving other carboxyl functions that might be available is preluded by preliminary ester development. Please note that esters are weaker acylating agents than either acyl halides or anhydrides.

Lastly, dicyclohexylcarbodiimide (DCC) impacts the desiccation of an amine and carboxylic acid combination to the corresponding amide under partially gentle conditions.

Peptide Synthesis Procedure

Peptide synthesis most frequently happens by joining the carboxyl category of the incoming amino acid to the N-terminal of the developing peptide chain. 

This C-to-N amalgamation is opposed to protein bio amalgamation, in the course of which the N-terminal of the approaching amino acid is connected to the C-terminal of the enzyme chain (N-to-C).

Because of the complicated character of in vitro protein amalgamation, the inclusion of amino acids in the developing chain happens in an exact, stepwise, and cyclical way.

While the typical techniques of peptide amalgamation have some distinct variation, they all adhere to a similar stepwise technique to include amino acids one-at-a-time to the developing peptide chain:

  • Deprotection- here, you must clear off the amino acid preservative class in Fmoc shielded monomers and columns with an alkaline solvent or piperidine.
  • Activation and cross-linking- an activator switches on the carboxyl category of the following amino acid. A peptide link is created via the reaction between the free amino group and the activated monomer. 
  • Elution and deprotection- the peptide is diluted from the column, and its protecting group is deprotected and diluted by a deprotection agent (TFA).

Peptide Synthesis Techniques

Besides the protein synthesis process, it helps if you can also learn the peptide amalgamation methods. They are:

  • Acyl azide method
  • Acid anhydride technique
  • Symmetric anhydride method
  • Mixed acid anhydride method

Benefits of Peptide Amalgamation

There are countless benefits of peptide synthesis. Some of them are:

Peptides Can Act as Medicines Against Specific Illnesses, Including Cancer

Peptide amalgamation can resemble organically occurring peptides, behaving like drugs to combat particular diseases, including cancer.

It Helps Cannabis-Derived Drugs Ease Pain Without Side Effects

Researchers have developed a peptides family that allows delta-9-tetrahydrocannabinol (THC), the main component of Cannabis sativa, to fight pain without side effects. Cannabis-derived drugs such as CBD are most used in pain relieving but have certain side effects like memory loss. The use of peptides in THC breaks the bonding between two receptors (cannabinoid type 1 and serotonin) and thus overcome the side effects.

It Plays a Crucial Part in MS Discovery

Researchers use the peptide synthesis process in mass spectrometry (or MS) applications.

This assists in serving as early biomarkers for disease. It can help in fighting diseases as well.


Peptide synthesis is a crucial but fragile process. To carry it out successfully, you have to be patient and willing to take your time.

It may seem challenging if you’re new to it, but it becomes second nature to you as you keep performing it.

Give it a try today and be a part of the countless scientists worldwide changing the world a day at a time through peptide amalgamation.

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