What Is a Peptide?

A peptide is a naturally occurring or synthetic compound made up of two or more amino acids linked by peptide bonds. These bonds form when the carboxyl group (C-terminus) of one amino acid reacts with the amino group (N-terminus) of another in a condensation reaction, releasing a water molecule. The result is a covalent amide bond (–CO–NH–) that creates a peptide chain.

The word “peptide” originates from the Greek term peptós, meaning “to digest.” Peptides are fundamental to biochemistry, existing throughout living organisms where they act as messengers, regulators, and structural units. Thousands of peptides occur naturally in the human body and in animals, while many more are regularly discovered or synthesized in laboratories. These discoveries continue to fuel promising areas of research, especially in molecular biology, cellular repair, and biochemical development.

How Are Peptides Formed?

Peptides are created both naturally within living systems and synthetically through laboratory methods:

• Endogenous formation: The body naturally produces peptides, including ribosomal peptides (made during protein translation) and non-ribosomal peptides (assembled by enzyme complexes).
• Laboratory synthesis: Modern peptide chemistry allows researchers to design and produce nearly limitless sequences using methods like liquid-phase peptide synthesis or the more widely used solid-phase peptide synthesis (SPPS). SPPS has become the gold standard due to its efficiency, precision, and scalability.

Historical Perspective

The study of peptides has a long scientific history. In 1901, Emil Fischer and Ernest Fourneau reported the first synthetic peptide. Later, in 1953, Vincent du Vigneaud successfully synthesized oxytocin, marking a major milestone in peptide chemistry and earning a Nobel Prize in Chemistry for his achievements.

Peptide Terminology

Peptides are classified by their amino acid length:

• Dipeptides: 2 amino acids
• Tripeptides: 3 amino acids
• Oligopeptides: Short sequences of fewer than 10 amino acids
• Polypeptides: Typically longer chains of more than 10 amino acids
• Proteins: Chains often exceeding 40–50 amino acids that fold into complex structures

Although length is the main factor distinguishing peptides from proteins, exceptions exist. Some smaller proteins, such as insulin, are commonly referred to as peptides, while certain longer chains, like amyloid beta, retain the peptide label in specific contexts.

Classification of Peptides

Peptides can be divided into several categories based on their origin and method of production:

Ribosomal Peptides

Generated through the translation of mRNA, ribosomal peptides frequently act as hormones or signaling molecules. Examples include vasoactive intestinal peptides, tachykinins, opioid peptides, pancreatic peptides, and calcitonin. Many undergo proteolysis, a process that cleaves larger precursors into smaller, active peptides.

Non-Ribosomal Peptides

Produced by enzyme systems rather than ribosomes, non-ribosomal peptides often display highly complex structures and are frequently cyclic. They occur widely in plants, fungi, and microorganisms. A notable example is glutathione, an important antioxidant in aerobic organisms.

Milk-Derived Peptides and Peptones

Milk peptides result from the breakdown of milk proteins, either through enzymatic digestion or fermentation by bacteria such as lactobacilli. Peptones, partially digested protein products, are commonly used as nutrient sources in microbiological research.

Peptide Fragments

Fragments can occur naturally during metabolic degradation or be generated intentionally in laboratories. Controlled enzymatic breakdown is often used for analysis and mapping studies.

Important Peptide Terms

• Amino Acids: The organic molecules containing amine and carboxyl groups that serve as the building blocks of peptides.
• Cyclic Peptides: Peptides whose amino acid sequence forms a ring structure. Examples include melanotan-2 and PT-141 (Bremelanotide).
• Peptide Sequence: The specific order of amino acids in a chain, also known as its primary structure.
• Peptide Bond: The covalent amide linkage formed between amino acids during condensation reactions.
• Peptide Mapping: Analytical methods that use enzymatic digestion and chromatographic analysis to identify or confirm peptide sequences.
• Peptide Mimetics: Compounds designed to mimic the biological functions of peptides, which may be natural or synthetic analogs.
• Peptide Fingerprint: A distinctive chromatographic or spectral pattern created when a peptide is hydrolyzed and mapped.
• Peptide Library: Large collections of systematically varied peptides used to study structure-activity relationships and binding properties.

Peptide Synthesis Methods

Laboratory synthesis has advanced significantly over the past century, with two major approaches:

• Solid-Phase Peptide Synthesis (SPPS): The most common method today. Peptides are built step-by-step on a solid resin, allowing precise assembly, efficient purification, and scalability.
• Liquid-Phase Peptide Synthesis (LPPS): An older but still useful method for certain applications, though it is less efficient for complex sequences.

Following synthesis, peptides are typically purified by high-performance liquid chromatography (HPLC) and characterized using mass spectrometry to confirm identity and purity. For stability, they are often lyophilized (freeze-dried), resulting in a crystalline structure suitable for research use.

Applications in Research

Research into peptides continues to grow, with studies exploring their roles in:

• Tissue repair and regeneration
• Metabolism and energy balance
• Anti-aging and longevity research
• Skin and hair health
• Immune signaling and inflammation regulation