What Are Peptides
Peptides are short chains of amino acids, typically consisting of 2-50 amino acid residues linked together by peptide bonds, with molecular weights generally less than 10 kDa. 1, 2
Fundamental Structure and Classification
Peptides are biopolymers that occupy a unique chemical space between small molecules and larger proteins, distinguishing them based on 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, 2
These molecules are biosynthesized either ribosomally by cellular machinery or through non-ribosomal enzymatic pathways, and can be arranged as linear chains or cyclic structures with various post-translational modifications, unusual amino acids, and stabilizing structural motifs. 2, 3
Biological Functions and Physiological Roles
Beyond their nutritional properties, peptides serve as structural components of hormones, enzymes, toxins, and antibiotics, playing fundamental physiological roles throughout the body including intrinsic signaling molecules such as neuropeptides and peptide hormones for cellular and interspecies communication. 1, 2
Peptides function as defense molecules to fend off enemies and microorganisms, as toxins to catch prey, and regulate gene expression and protein synthesis across diverse organisms including plants, microorganisms, insects, birds, rodents, primates, and humans. 2, 4
Short peptides consisting of 2-7 amino acid residues can penetrate cell nuclei and nucleoli to interact with nucleosomes, histone proteins, and both single- and double-stranded DNA, regulating template-directed synthetic reactions, replication, transcription, and DNA repair through DNA-peptide interactions and sequence recognition in gene promoters. 4
Therapeutic and Clinical Applications
Since the introduction of insulin as the first commercial peptide drug, more than 80 peptide-based drugs have reached the market for conditions including diabetes, cardiovascular diseases, and urological disorders, with over 150 currently in clinical development. 1, 2
The first peptide corticotropin was approved by the FDA in 1952 for multiple inflammatory diseases and West syndrome, establishing peptides as viable therapeutic agents. 5
Peptides are gaining clinical popularity as biomarkers and innovative therapeutics due to their advantages including low toxicity compared to long-chain peptides, though challenges remain regarding chemical and physical stability, short circulating plasma half-life, and solubility issues. 1, 2, 6
Specialized Peptide Classes
Ribosomally synthesized and post-translationally modified peptides (RiPPs) represent a major class where precursor peptides undergo extensive enzymatic modifications including cyclization, heterocycle formation, and various chemical transformations guided by leader peptide sequences and recognition sequences. 3
Examples of specialized peptides include methanobactins (copper chelators), quorum sensing compounds like ComX, and N-formylated peptides that serve specific biological functions such as chemoattractants for neutrophils or protection from aminopeptidases. 3
In therapeutic applications, oligopeptides are designed to target cellular proteins, particularly cell surface receptors, such as somatostatin analogues (14 or 28 amino acids) used in peptide receptor radionuclide therapy for neuroendocrine tumors. 3
Pharmacokinetic Considerations
Intrinsic factors (age, gender, renal and hepatic impairment) and extrinsic factors (drug-drug interactions, food, smoking, alcohol) can influence peptide pharmacokinetics, though their impact on peptides differs substantially from small molecules and requires specific assessment during drug development. 5
Peptide properties including binding potential, half-life, transmembrane patterns, stability, charge, isoelectric point, and molecular weight can be predicted using sequence-based computational tools to assist in pharmaceutical development and optimization. 6