What are peptides?

What Are Peptides?

Peptides are short chains of amino acids linked together by peptide bonds, typically consisting of 2-50 amino acids with a molecular weight less than 10 kDa, that serve various biological functions in the body. 1

Structure and Classification

Peptides occupy a unique chemical space between small molecules and larger proteins:

• Size-based classification:

  • Oligopeptides: Fewer than 10-20 amino acids
  • Polypeptides: More than 20 amino acids
  • Proteins: Usually more than 50 amino acids, often containing multiple peptide subunits 1

• Structure types:

  • Linear chains
  • Cyclic structures
  • Modified with post-translational modifications
  • May contain unusual amino acids and stabilizing motifs 2

Biological Origin and Synthesis

Peptides can be produced through several mechanisms:

• Ribosomal synthesis: Produced by cellular ribosomal machinery, often as larger precursor peptides that undergo post-translational modifications 3

  • Example: Many peptides start as precursor peptides with a leader peptide and core peptide region

• Non-ribosomal synthesis: Produced by specialized enzymes without using ribosomes 2

• Post-translational modifications: Many peptides undergo extensive modifications after synthesis, including:

  • Cyclization
  • Disulfide bond formation
  • Hydroxylation
  • Methylation
  • N-terminal modifications (acetylation, formylation) 3

Biological Functions

Peptides serve numerous critical functions in the body:

• Signaling molecules: Act as hormones, neurotransmitters, and cell-signaling entities 4

  • Example: Insulin, a peptide hormone crucial for glucose regulation

• Immune regulation: Many peptides play roles in immune system function 5

• Antimicrobial activity: Some peptides serve as natural defense molecules against microorganisms 2

• Gene expression regulation: Short peptides can penetrate cell nuclei and interact with DNA to regulate gene expression 5

• Enzymatic functions: Some peptides function as enzymes or enzyme components 1

Medical and Therapeutic Applications

Peptides have significant clinical importance:

• Pharmaceutical applications: More than 60 peptide drugs have been FDA-approved with over 150 in clinical development 2

  • Example: Glatiramer acetate, a synthetic polypeptide containing L-glutamic acid, L-alanine, L-tyrosine, and L-lysine, used in multiple sclerosis treatment 6
  • Example: Somatropin, a recombinant human growth hormone peptide 7

• Vaccine development: Peptides are used in vaccine design, particularly for cancer immunotherapy 3

  • Synthetic long peptides (SLPs) of 15-30 amino acids are effective neoantigen delivery mechanisms 3

• Diagnostic biomarkers: Peptides serve as important biomarkers for various diseases 2

Pharmacokinetic Considerations

Peptide drugs have unique pharmacokinetic properties:

• Absorption and distribution: Generally limited by size and hydrophilicity
• Metabolism: Often rapidly degraded by peptidases
• Elimination: Typically through renal clearance
• Intrinsic and extrinsic factors: Age, gender, disease states, and drug interactions can affect peptide pharmacokinetics 8

Common Challenges with Peptide Therapeutics

• Manufacturability issues: Chemical properties like hydrophobicity, presence of cysteine residues, and asparagine-proline bonds can make synthesis difficult 3
• Stability concerns: Many peptides have short half-lives due to enzymatic degradation
• Delivery challenges: Poor membrane permeability often limits bioavailability 3

Peptides represent an important class of biomolecules with diverse functions and growing therapeutic potential. Their unique position between small molecules and proteins gives them distinct advantages in drug development, including high specificity, low toxicity, and the ability to target previously "undruggable" protein-protein interactions.