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Peptide Synthesis: Advantage Of Solid Phase Peptide Synthesis

Scientists use peptides to design novel enzymes, make epitope-specific antibodies, and map antibody epitopes and enzyme tying sites.

Peptide synthesis was the primary method of synthesizing proteins before. Now, thanks to technology, experts have introduced solid-phase peptide synthesis.

Countless biological procedures’ control and regulatory mechanisms rely on proteins and peptides obtained from a-amino acids.

Additionally, researchers produce many contemporary medications from derivatives of peptides or peptides. Peptide chemistry and a-amino acids have become central automation in:

  • Medicinal chemistry
  • Organic chemistry
  • Biotechnology
  • Biochemistry

Here’s where peptide synthesis companies come in. Is solid-phase peptide synthesis any different from peptide synthesis? What are its benefits? Keep reading to find out.

What Exactly is Peptide Synthesis?

It’s the creation of a peptide bond between several amino acids. A peptide usually refers to flexible (tiny secondary structure) chains of approximately thirty to fifty amino acids.

How Peptide Synthesis Assists the Medical Sector

Thanks to peptide synthesis, scientists have extracted several biological substances from their natural environment and produced them in a laboratory.

That’s how they make vaccines for diseases such as:

  • The flu
  • Measles
  • Mumps
  • Rubella
  • Herpes zoster (shingles)
  • Hepatitis A.

In addition, peptide synthesis aids healthcare workers in making other vaccines like the Hepatitis B vaccine.

Medications like insulin and vasopressin (ADH) that address metabolic disorders like diabetes mellitus and congestive heart failure also derive from peptide synthesis methods. What’s more, scientists use peptides to treat diseases such as multiple sclerosis, chronic inflammatory disorders, and cancer.

What Goes on in Peptide Synthesis?

The procedure involves four main methods:

Peptide Deprotection

It entails detaching the protecting group (tert-butyloxycarbonyl) from the C-terminal of the peptide using trifluoroacetic acid.

The process allows researchers to apply other chemical reagents such as ninhydrin and dansyl chloride that react with amino acids like lysine and tyrosine. The trifluoroacetic acid will also remove the C-terminal protecting group.

Coupling of Amino Acids

It entails using activated carboxyl groups on amino acid derivatives and coupling reagent N, N’ dicyclohexylcarbodiimide (DCC).

While different types of amino acids require various activation strategies, the most popular include:

  • Activating Alanine with IBCF
  • Activating Arginine and Lysine with HATU
  • Activating Asparagine and Glutamine with PyBOP
  • Activating Aspartic Acid and Glutamic Acid with TBTU while activating the side chain of cysteine, tyrosine, and histidine using IBCF.

Cleavage of Peptides

After continuous rounds of acid linking and deprotection, you should remove all residual shielding categories in the nascent peptides.

Experts use acidolysis to cleave these groups. The substance they use for cleavage depends on the shielding scheme used. They’ve used strong acids such as:

  • Trifluoromethane sulfonic acid (TFMSA)
  • Hydrogen fluoride (HF)
  • Hydrogen bromide (HBr) to cleave Bzl and Boc groups.

Peptide Purification

Finally, they purify the peptide using chromatography or recrystallization. You should note that most of this process occurs in different locations under peculiar conditions.

Solid-Phase Peptide Synthesis

In solid-phase peptide synthesis (SPPS), researchers use solid support and link amino acids singly and successively to it.

The process starts with attaching an N-terminal protecting group such as tert-butyloxycarbonyl (Boc) to the resin on the solid phase. An N-terminal deprotection solution then removes the protecting group. The next step requires coupling each amino acid to the resin via an active ester that enables reactions between carboxylic acids and alcohols.

Afterward, the excess reagents are washed away using solvents such as ethyl acetate and dimethylformamide (DMF). Finally, an N-terminal deprotection solution removes the tert-butyloxycarbonyl group.

Benefits of Solid-Phase Peptide Synthesis

There are several advantages of SPPS over other peptide synthesis methods:

High Yields with Fewer Steps

SPPS allows for high yields in fewer steps. This results in cost and time savings. Furthermore, the process doesn’t require advanced chemistries that are difficult to transfer.

Diffusing Reagents Create Clean Product

Experts use reagents that diffuse into the resin and peptide to avoid side reactions or irreversible reactions between chemicals used in SPPS. These reagents include solvents such as DMF, DMSO, and ethyl acetate.

Solid Phase Support Allows for Modification of Peptides

Experts can use solid supports to modify peptides after synthesis using solution chemistry. For instance, they can attach different residues, linkers, protecting groups, fluorescent tags, etc.

This allows researchers to synthesize peptides with modified functional groups, such as p-Nitroaniline and 2-aminoethyl Methacrylate.

The process will enable the synthesis of peptides with low melting points and increased solubility in water.

More Resin for More Productivity and Greater Variety

SPPS successfully links on average three amino acids per cycle, which presents more opportunities to produce more peptides with high yields than other methods that only link one amino acid per cycle.

Greater Peptide Diversity

In addition, researchers can link various types of amino acids with different side chains to generate libraries containing a wider diversity. This leads to producing a myriad of peptides with different properties and applications. What’s more, SPPS affords greater reproducibility compared to other methods due to its standardization.


SPPS provides a clean, versatile synthesis of peptides. Researchers can use solid supports for quick modification and purification of peptides, which affords better yields and greater diversity. The key to using it effectively is learning how it works and taking your time during the process.

You’ll be surprised by how straightforward and effective it is for all your peptide-related experiments. Try solid-phase peptide synthesis today if you haven’t already and discover its advantages firsthand.

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