Synthetic Peptide Synthesis

synthetic peptide

Synthetic peptide occupies an interesting space along the molecular continuum between traditional small molecule drugs made through chemical synthetic routes and larger biologics (proteins) made through recombinant DNA technology in living organisms. Primarily made of amino acids strung together in a sequence, therapeutic peptides range in length from a few to over 70 amino acid residues.

Peptide synthesis can be accomplished either by solution or solid-phase coupling (SPC) methods. Both have their advantages and disadvantages. In the solution method, short peptide sequences are first synthesized in a solution and then coupled together using a standard coupling procedure. This approach requires a significant number of reactions and a high degree of skill. It can be time consuming and labor intensive.

In contrast, SPPS is a more streamlined process. This involves binding the first N-protected amino acid to a solid polymer (usually a cyclohexyl- or dicyclohexyl-sufonate) through an amide bond. This steric block prevents further reaction of the carboxyl groups of subsequent amino acids with the polymer. Once the peptide is complete, the polymer is removed and the peptide is then cleaved from the carboxyl groups with an acid, such as trifluoroacetic acid (TFA).

The success of any SPPS process is dependent upon a number of factors. These include the choice of a solid support, appropriate coupling reagents, and an efficient method for cleaving the peptide from the support. Also of importance, it is critical that all steps be performed in a controlled manner to minimize side reactions. The advent of high-performance liquid chromatography (HPLC; UNIT 11.6) has been a boon to the modern peptide synthesis laboratory, because this technique makes it easy to identify and remove systematic low-level by-products that accrue during chain assembly and upon cleavage of the peptide.


If you are interested in consuming peptides, it is imperative to consult a medical professional! If any action is taken as a result of this content, we cannot be held liable for any damages. Click on the icon to learn more about why a medical consultation is mandatory!

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