What is a Peptide?
A peptide is a short chain of amino acids linked together by peptide bonds, typically consisting of 2 to 50 amino acids with a molecular weight less than 10 kDa. 1, 2
Fundamental Structure and Definition
Peptides are distinguished from proteins primarily by their size: oligopeptides contain fewer than 10-20 amino acids, polypeptides contain more than 20 amino acids, while proteins typically consist of more than 50 amino acids and often contain multiple peptide subunits. 1
The defining characteristic is the peptide bond, which is the chemical linkage connecting amino acids in a specific sequence. 1, 3
The shorter chain length of peptides is the key feature that differentiates them from larger protein molecules. 1
Biological Significance
Beyond their role as nutritional components, peptides serve as structural components of hormones, enzymes, toxins, and antibiotics, playing fundamental physiological roles throughout the body. 1
Peptides regulate functions across multiple systems including the endocrine, nervous, and immune systems. 4
Short peptides (2-7 amino acid residues) can penetrate cell nuclei and nucleoli, interacting with nucleosomes, histone proteins, and both single- and double-stranded DNA to regulate gene expression and protein synthesis. 4
Classification Systems
Peptides can be categorized using several approaches: 3
- By chain length: distinguishing oligopeptides from polypeptides
- By source: natural versus synthetic origin
- By biological function: hormonal, enzymatic, antimicrobial, etc.
Therapeutic Applications
More than 60-80 peptide-based drugs have been approved by the FDA since the first peptide drug (corticotropin) was approved in 1952, with over 140 peptide therapeutics currently in clinical trials. 2, 5
Peptides are recognized for being highly selective, efficacious, relatively safe, and well-tolerated compared to small molecule drugs. 5
FDA-approved peptide drugs treat conditions including diabetes, cardiovascular diseases, urological disorders, inflammatory diseases, and obesity. 1, 2
Tirzepatide is a synthetic peptide with dual-hormone agonistic activity at both GLP-1 and GIP receptors, demonstrating the therapeutic potential of engineered peptides. 6
Specialized Peptide Categories
Ribosomally synthesized and post-translationally modified peptides (RiPPs) represent a diverse class where precursor peptides undergo enzymatic modifications after ribosomal synthesis, creating complex natural products with varied biological activities. 7
Some peptides serve as precursors to smaller bioactive molecules: for example, PqqA is a 22 amino acid peptide that undergoes oxidative modifications to produce pyrroloquinoline quinone (PQQ), a bacterial dehydrogenase cofactor. 7
Clinical Considerations
The efficacy of therapeutic peptides depends on precise molecular modifications that affect stability, half-life, and resistance to enzymatic degradation. 6
Peptides used in vaccine design, such as synthetic long peptides (SLPs) of 15-30 amino acids, require internalization and processing by professional antigen-presenting cells for optimal immune activation. 7
Manufacturing quality is critical: FDA-approved peptides undergo strict oversight ensuring guaranteed potency, sterility, and consistent molecular structure, which cannot be assured with compounded versions. 6