Peptides

Peptides
Definition Short chains of amino acids
Size Range 2-50 amino acids
Bond Type Peptide bonds
Related To Proteins, amino acids
Examples Insulin, oxytocin, endorphins

Peptides are short chains of amino acids linked by peptide bonds. They are distinguished from proteins primarily by their shorter length, typically containing between 2 and 50 amino acids. Peptides play crucial roles in biological processes, acting as hormones, neurotransmitters, growth factors, and signaling molecules throughout the body.

Structure and Formation

The Peptide Bond

Peptides are formed when the carboxyl group (-COOH) of one amino acid reacts with the amino group (-NH2) of another, releasing a water molecule (condensation reaction). The resulting covalent bond is called a peptide bond.

R₁-CH(NH₂)-COOH + H₂N-CH(R₂)-COOH → R₁-CH(NH₂)-CO-NH-CH(R₂)-COOH + H₂O

Classification by Size

Type Amino Acids Examples
Dipeptide 2 Carnosine, anserine
Tripeptide 3 Glutathione, TRH
Oligopeptide 2-20 Oxytocin (9), vasopressin (9)
Polypeptide 20-50 Insulin chains, ACTH
Protein >50 Hemoglobin, enzymes

Types of Peptides

Endogenous Peptides

Naturally produced peptides in the human body include:

Hormonal Peptides

  • Insulin: Regulates blood glucose (51 amino acids)
  • Glucagon: Raises blood glucose (29 amino acids)
  • Growth Hormone Releasing Hormone (GHRH): Stimulates GH release
  • Oxytocin: Social bonding, uterine contractions (9 amino acids)
  • Vasopressin (ADH): Water balance regulation (9 amino acids)

Neuropeptides

  • Endorphins: Natural pain relief, reward
  • Enkephalins: Pain modulation
  • Substance P: Pain transmission
  • Neuropeptide Y: Appetite regulation

Antimicrobial Peptides

  • Defensins: Innate immune defense
  • Cathelicidins: Broad-spectrum antimicrobials

Synthetic Peptides

Peptides created for research and therapeutic purposes:

  • BPC-157 – Research peptide for tissue healing
  • TB-500 – Synthetic thymosin beta-4
  • Semaglutide – Modified GLP-1 for diabetes/weight
  • Ipamorelin – Growth hormone secretagogue

Biological Functions

Cell Signaling

Peptides serve as critical messengers in cellular communication:

  • Bind to specific receptors on cell surfaces
  • Trigger intracellular signaling cascades
  • Regulate gene expression
  • Coordinate tissue responses

Hormonal Regulation

Many hormones are peptides that regulate:

  • Metabolism and energy balance
  • Growth and development
  • Reproduction
  • Stress responses
  • Water and electrolyte balance

Immune Function

Peptides play essential roles in immunity:

  • Direct antimicrobial activity
  • Immune cell communication (cytokines)
  • Inflammation regulation
  • Wound healing coordination

Research Applications

Research Peptide Categories

Growth Hormone Peptides

Compounds that stimulate growth hormone release:

Healing and Recovery Peptides

  • BPC-157 – Gastric-derived healing peptide
  • TB-500 – Thymosin beta-4 fragment

Metabolic Peptides

Peptide Synthesis

Solid-Phase Peptide Synthesis (SPPS)

The most common method for peptide production, developed by Bruce Merrifield (Nobel Prize, 1984):

  1. Anchor first amino acid to solid resin
  2. Sequentially add protected amino acids
  3. Remove protecting groups after each addition
  4. Cleave completed peptide from resin
  5. Purify using HPLC

Recombinant Production

Larger peptides and proteins are often produced using:

  • Bacterial expression (E. coli)
  • Yeast expression systems
  • Mammalian cell culture

Peptide Therapeutics

Peptides offer advantages as therapeutic agents:

Advantages

  • High specificity and potency
  • Lower toxicity than small molecules
  • Predictable metabolism
  • Fewer drug-drug interactions

Challenges

  • Poor oral bioavailability
  • Short half-life (enzymatic degradation)
  • Manufacturing complexity
  • Storage requirements (often refrigeration)

FDA-Approved Peptide Drugs

Drug Type Indication
Insulin Hormone Diabetes
Semaglutide GLP-1 agonist Diabetes, obesity
Tesamorelin GHRH analog HIV lipodystrophy
Octreotide Somatostatin analog Acromegaly, carcinoid
Leuprolide GnRH analog Prostate cancer, endometriosis

Handling and Storage

Peptides require careful handling:

  • Lyophilized (powder): Store at -20°C or colder, stable for years
  • Reconstituted: Refrigerate (2-8°C), use within weeks
  • Avoid: Repeated freeze-thaw cycles, heat, direct sunlight
  • Reconstitution: Use bacteriostatic water for multi-dose vials

References

  1. Nelson DL, Cox MM. "Lehninger Principles of Biochemistry." 8th ed. W.H. Freeman; 2021.
  2. Fosgerau K, Hoffmann T. "Peptide therapeutics: current status and future directions." Drug Discov Today. 2015.
  3. Lau JL, Dunn MK. "Therapeutic peptides: Historical perspectives, current development trends, and future directions." Bioorg Med Chem. 2018.