What are Peptides?

The Building Blocks: Amino Acids

At their most fundamental level, peptides are chains of amino acids. There are 20 standard amino acids that occur naturally in the human body, each consisting of a central carbon atom bonded to a carboxyl group ($COOH$), an amino group ($NH_2$), and a unique “R-group” or side chain that defines its specific chemical properties (StatPearls, 2024). When amino acids link together, they are referred to as residues because a molecule of water is lost during the bonding process, leaving behind only a “residue” of the original amino acid (StatPearls, 2024).

The Peptide Bond: A Chemical Bridge

The link between amino acids is a covalent chemical bond known as a peptide bond. This bond forms through a dehydration synthesis (or condensation) reaction, where the carboxyl group of one amino acid reacts with the amino group of another.

  • Bond Character: Unlike a standard single bond, the peptide bond has a partial double-bond character, making it shorter, stronger, and more rigid (StatPearls, 2024).

  • Planar Geometry: This rigidity prevents the bond from rotating freely, forcing the atoms into a flat, or “planar,” arrangement. This specific geometry is crucial because it dictates how the final peptide chain will fold and interact with other molecules.

  • Trans Configuration: Due to the physical space occupied by the side chains (R-groups), peptide bonds almost always form in a trans configuration, where the side chains are on opposite sides of the backbone to minimize interference (StatPearls, 2024).

Classification by Length (Nomenclature)

Peptides are categorized based on the number of amino acid residues in their sequence. This classification helps researchers distinguish between simple signaling molecules and complex biological structures.

  • Dipeptides & Tripeptides: The simplest forms, consisting of two or three amino acids, respectively.

  • Oligopeptides: Short chains typically containing between 10 and 20 amino acids (StatPearls, 2024).

  • Polypeptides: Longer, unbranched chains generally exceeding 20 amino acids (StatPearls, 2024).

  • Peptides vs. Proteins: While the terms are often used interchangeably, “peptide” usually refers to chains of 50 amino acids or fewer. Once a chain exceeds 50 residues and adopts a stable, three-dimensional folded shape, it is classified as a protein.

The “Middle Ground” Advantage

In the context of drug discovery and research, peptides occupy a unique “middle ground” between small-molecule drugs (like aspirin) and large biological proteins (like antibodies). They combine the high specificity and potency of large proteins with the lower toxicity and manageable manufacturing of smaller chemicals (Diller et al., 2015). This makes them ideal for targeting Protein-Protein Interactions (PPIs), which are often too large for small molecules to block but too small or inaccessible for traditional antibodies (Diller et al., 2015).

References

StatPearls. (2024). Biochemistry, Peptide. StatPearls – NCBI Bookshelf. https://www.ncbi.nlm.nih.gov/books/NBK562260/

Diller, D. J., Jarosinski, M., Sawyer, T. K., & Audie, J. (2015). Peptide drug discovery: innovative technologies and transformational medicines. Advances in the Discovery and Development of Peptide Therapeutics, 8-27. https://doi.org/10.4155/fseb2013.14.105