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Intro to Therapeutic Peptides

Intro to Therapeutic Peptides

What is a Peptide?

A peptide is a naturally occurring chemical compound that consists of two or more amino acids linked together by peptide bonds. These bonds are covalent, formed when the carboxyl group (C-terminus) of one amino acid reacts with the amino group (N-terminus) of another through a condensation reaction, during which a molecule of water is expelled. The bond that results, a CO-NH linkage, is also known as an amide bond, and it forms the backbone of peptides and proteins.

Origin of the Term

The word “peptide” is derived from the Greek πέσσειν, meaning “to digest.” This etymology reflects the fundamental role peptides play in digestion and biological processes. Peptides are ubiquitous in both human and animal bodies, performing essential functions in various biochemical pathways. Their discovery and continued synthesis in laboratories promise significant advancements in health care and pharmaceuticals.

Formation of Peptides

Peptides can be produced naturally within the body or synthesized artificially in a lab. Naturally, peptides are generated by the ribosomal translation of messenger RNA (mRNA), resulting in ribosomal peptides that act as hormones and signaling molecules. Alternatively, non-ribosomal peptides are created by specific enzymes and can sometimes have complex cyclic structures. In the laboratory, techniques such as liquid phase peptide synthesis and the more commonly used solid phase peptide synthesis (SPPS) allow for the creation of a wide range of peptides. These synthetic methods are vital for research and the development of peptide-based therapies.

Historical Milestones

The journey of peptide science began with the synthesis of the first peptide in 1901 by Emil Fischer and Ernest Fourneau. This pioneering work set the stage for later breakthroughs, including the synthesis of oxytocin in 1953 by Vincent du Vigneaud, marking one of the first major successes in peptide synthesis.

Peptide Classification

Peptides are categorized based on the number of amino acids they contain. For example:

  • Dipeptides: Composed of two amino acids.
  • Tripeptides: Consist of three amino acids.
  • Oligopeptides: Short peptides generally having fewer than ten amino acids.
  • Polypeptides: Longer chains that typically consist of more than ten amino acids.
    Peptides that are longer than 40 to 50 amino acids are usually classified as proteins. However, there are exceptions; some longer peptides, such as amyloid beta, are considered proteins, while some smaller proteins, like insulin, are often referred to as peptides.

Diverse Types of Peptides

Peptides are further divided based on their origin and structure:

  • Ribosomal Peptides: Produced through mRNA translation and often involved in hormonal and signaling roles. These peptides can undergo proteolysis to reach their mature forms.
  • Non-Ribosomal Peptides: Generated by enzyme systems rather than ribosomes, frequently forming cyclic structures, and commonly found in plants, fungi, and microorganisms. An example is glutathione, which plays a critical role in antioxidant defense.
  • Milk Peptides: Derived from milk proteins, typically formed during digestion or fermentation by lactobacilli.
  • Peptones: These are peptides resulting from the enzymatic digestion of animal milk or meat and are widely used in laboratory media to cultivate fungi and bacteria.
  • Peptide Fragments: Often produced during controlled laboratory enzymatic degradation, though they can also form naturally.

Key Peptide-Related Terminology

  • Amino Acids: The building blocks of peptides, each containing both an amine and a carboxyl group.
  • Cyclic Peptides: Peptides that form a closed ring structure, such as melanotan-2 and PT-141 (Bremelanotide).
  • Peptide Sequence: The specific order of amino acids linked by peptide bonds.
  • Peptide Mapping: A method used to determine or verify the sequence of a peptide or protein by enzymatic fragmentation and subsequent analysis.
  • Peptide Mimetics: Molecules that imitate the function of bioactive peptides, whether natural or synthetically modified.
  • Peptide Fingerprint: A chromatographic pattern obtained by partial hydrolysis and two-dimensional mapping of a peptide.
  • Peptide Library: A collection of peptides with systematically varied amino acid sequences, often generated using solid phase peptide synthesis for research and pharmaceutical purposes.
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