What Are Peptides?

Definition and Basic Structure

Peptides are short chains of amino acids, typically containing between 2 and 50 amino acids, linked together by peptide bonds formed through dehydration synthesis reactions. They are distinguished from proteins primarily by size—proteins generally contain more than 50 amino acids and exhibit complex tertiary or quaternary structures. The peptide bond forms between the carboxyl group (-COOH) of one amino acid and the amino group (-NH2) of another, releasing a water molecule. This creates a planar, rigid bond with partial double-bond character due to resonance.

Classification by Size

Peptides are commonly classified by the number of amino acid residues: dipeptides (2 amino acids), tripeptides (3), oligopeptides (2-20), and polypeptides (20-50+). The boundary between polypeptides and proteins is not absolute but generally occurs around 50 amino acids or ~5,000 Daltons molecular weight. Some researchers use 100 amino acids as the cutoff. Biologically active peptides range from tiny dipeptides like carnosine to larger polypeptides like insulin (51 amino acids).

Structural Features

Peptide structure is described at four levels: primary (amino acid sequence), secondary (local folding patterns like alpha-helices and beta-sheets), tertiary (3D shape), and quaternary (multi-subunit assembly). Most small peptides lack stable tertiary structure in solution, existing as flexible, random-coil conformations. However, cyclic peptides, disulfide-bridged peptides, and those with D-amino acids or other modifications may adopt defined conformations that enhance receptor binding and stability.

Endogenous Peptides

The human body produces thousands of endogenous peptides serving diverse functions: hormones (insulin, glucagon, growth hormone-releasing hormone), neurotransmitters/neuromodulators (enkephalins, substance P, neuropeptide Y), antimicrobial defense (defensins, cathelicidins), signaling molecules (cytokines, growth factors), and structural components. These peptides are synthesized ribosomally from mRNA or through non-ribosomal peptide synthesis, and are typically processed from larger precursor proteins through proteolytic cleavage.

Synthetic Peptides in Research

Synthetic peptides are produced through solid-phase peptide synthesis (SPPS) developed by Bruce Merrifield (Nobel Prize 1984) or solution-phase synthesis. Modern SPPS using Fmoc (fluorenylmethyloxycarbonyl) chemistry can produce peptides up to 50+ amino acids with high purity. Research peptides serve as tools to study receptor pharmacology, enzyme kinetics, protein-protein interactions, and cellular signaling pathways. They are also used as antigens to generate antibodies, as standards in bioanalytical methods, and as starting points for drug development.

Peptide Nomenclature

Peptides are named using the three-letter or one-letter amino acid codes (e.g., Gly-Ala-Val or GAV). The N-terminus (free amino group) is conventionally written on the left, and the C-terminus (free carboxyl group) on the right. Modified peptides use additional notation: Ac- (N-terminal acetylation), -NH2 (C-terminal amidation), D- prefix (D-amino acids), and various codes for non-natural amino acids. Cyclic peptides indicate the cyclization sites in parentheses.

Key Takeaways