Inside the World of Research Peptides – How They’re Made

The Science Behind Peptide Synthesis

Peptides are composed of amino acids joined by peptide bonds. In nature, these bonds are formed during protein synthesis, where DNA is transcribed to mRNA and then translated by ribosomes. However, for research purposes, peptides are chemically synthesized in the lab to allow precise control over their sequence, structure, and modifications.

One of the most widely used laboratory techniques is Solid Phase Peptide Synthesis (SPPS), developed in 1963 by Bruce Merrifield. SPPS revolutionized peptide manufacturing by attaching the growing peptide chain to a solid resin, allowing repeated addition of amino acids while simplifying purification.

Step-by-Step: How Research Peptides Are Made

The synthesis of research peptides follows several critical steps. Here’s a simplified overview:

1. Resin Attachment
   • The first amino acid is preloaded onto a solid resin, forming the foundation of the peptide chain.
   • The resin allows the peptide to remain immobilized while solvents and reagents are applied.
2. Deprotection
   • Amino acids have protecting groups such as Fmoc on the amine side to prevent unwanted reactions.
   • Deprotection removes the Fmoc from the first amino acid, exposing the reactive site for the next amino acid.
3. Coupling Reaction
   • The next amino acid is added along with coupling reagents, linking the free amine to the carboxyl group of the previous amino acid.
   • This step is repeated sequentially until the entire peptide chain is assembled.
4. Cleavage and Purification
   • After synthesis, the peptide is cleaved from the resin using strong acids such as trifluoroacetic acid (TFA).
   • Purification is performed via High-Performance Liquid Chromatography (HPLC) and mass spectrometry to ensure correct sequence and high purity.

Optional Bullets for Lab Notes:

• Protecting groups prevent side reactions and branching.
• Automated synthesizers allow precise control over synthesis cycles.
• Lab conditions are rigorously monitored for temperature, humidity, and chemical purity.