What are peptides? Functions, Types & Synthesis Methods

Peptides are short chains of amino acids, the building blocks of proteins. While they may be small-sized, peptides play essential roles in the human body by acting as hormones, enzymes, and signaling molecules. Recently, peptides have gained attention for their therapeutic potential, leading to a growing interest in peptide synthesis and peptide manufacturing.

Functions of Peptides

Peptides are involved in a wide range of biological functions:

• Hormones: Peptides-like insulin regulate vital processes such as blood sugar levels.
• Enzymes: Some peptides function as enzymes, helping to accelerate biochemical reactions in the body.
• Signaling Molecules: Peptides often act as messengers, transmitting signals between cells to regulate activities like growth, immune response, and metabolism.

Therapeutic Applications of Peptides

Due to their natural roles in the body, peptides are being explored as therapeutic agents for treating various diseases. Some of their notable applications include:

• Cancer Treatment: Peptide-based drugs can target cancer cells specifically, reducing the side effects of traditional chemotherapy.
• Diabetes Management: Synthetic peptides like insulin analogs help in managing blood sugar levels in people with diabetes.
• Infectious Diseases: Certain peptides are being developed as antimicrobial agents to fight bacterial infections.
• Cardiovascular Diseases: Peptides can help regulate blood pressure and prevent blood clotting, offering potential treatments for heart disease.

Advantages of Peptide Drugs

Peptides offer several benefits in drug development compared to traditional small molecules or biologics:

• High Specificity: Peptides can target specific receptors in the body with high accuracy, reducing unwanted side effects.
• Natural Degradation: Since peptides are naturally occurring, they are broken down into amino acids by the body, which minimizes the risk of long-term toxicity.
• Shorter Development Time: The smaller size and simpler structure of peptides can make them easier and faster to develop compared to larger biologics like proteins.

Peptide Synthesis: How Peptides Are Made

Peptide synthesis is the process of chemically creating peptides by linking amino acids together in a specific sequence, , typically utilizing either solid-phase peptide synthesis (SPPS) or liquid-phase synthesis methods. The process involves stepwise elongation of the peptide chain, with each amino acid being activated and coupled to the growing chain, followed by deprotection of functional groups to facilitate subsequent coupling. This method allows for the precise synthesis of peptides for use in research, drug development, and other biotechnological applications.

• Solid-Phase Synthesis: This is the most common method, where the peptide synthesis begins by attaching the initial amino acid on a solid support and then adding the subsequent amino acid residues to the first one, making it easier to control the sequence and purity of the resultant peptide.
• Solution-Phase Synthesis: This method is often more efficient for shorter peptides, usually up to 20 amino acids. Amino acids are dissolved in a liquid solution and chemically reacted to form peptide bonds. Solution-phase synthesis provides greater flexibility in design and can be advantageous for achieving higher purity or for peptides requiring specialized chemical modifications

Challenges in Peptide Drug Development

Despite their potential, peptide drugs come with certain challenges:

• Stability: Peptides can be rapidly degraded in the body by proteolytic enzymes, which can significantly reduce their therapeutic effectiveness.
• Delivery: Peptides often lack stability necessary for oral administration, necessitating the use of injections or alternative delivery methods to ensure adequate bioavailability.
• Manufacturing Costs: Large-scale peptide manufacturing can be expensive due to the complex processes involved in their synthesis.

Solutions to Overcome Peptide Drug Development Challenges

To address the challenges in peptide drug development, researchers and manufacturers are working on innovative solutions:

1) Stability

• Chemical Modifications: To enhance peptide stability and prevent enzymatic degradation, peptides can be modified by incorporating non-natural amino acids, D-amino acids, or cyclic structures. These modifications reduce the rate of hydrolysis and proteolysis, thereby prolonging their half-life.
• PEGylation: Adding polyethylene glycol (PEG) chains to peptides can improve stability by protecting them from proteases, enhancing solubility, and reducing immunogenicity. PEGylation also prolongs circulation time in the bloodstream.
• Protease Resistance: Designing peptides with resistance to proteolytic cleavage can be achieved through structural modifications (e.g., incorporating unnatural amino acids or cyclic peptide backbones) to reduce degradation by enzymes in the body.
• Stabilizing Conjugates: Peptides can be conjugated to stabilizing agents such as nanoparticles or liposomes, which provide physical protection from enzymatic breakdown and improve their therapeutic efficacy.

2) Delivery

• Nanoparticles and Liposome Encapsulation: Encapsulating peptides in nanocarriers like lipid nanoparticles or liposomes can improve stability and protect the peptides from degradation while enhancing targeted delivery to specific tissues or cells.
• Oral Delivery Systems: Oral peptide delivery faces challenges like degradation in the gastrointestinal tract. Solutions include formulating peptides with absorption enhancers (e.g., surfactants, fatty acids) or using nanoparticles to facilitate uptake across the gut wall.
• Peptide-Polymer Conjugates: By conjugating peptides to biocompatible polymers, it’s possible to enhance solubility, improve stability, and extend release profiles, making them more effective and easier to administer.
• Transdermal and Inhalation Delivery: Innovative delivery methods like transdermal patches or inhalable formulations can bypass the gastrointestinal system entirely, providing alternative routes for peptide absorption and improving bioavailability.
• Half-life Extension Technologies: Techniques like conjugation to albumin-binding peptides, or fusion with long-lived proteins (e.g., antibodies), can extend the peptides’ half-life in the bloodstream, reducing the need for frequent dosing.

3) Manufacturing Costs

• Solid-Phase Peptide Synthesis (SPPS) and Automation: Advances in SPPS technology, including automated synthesis platforms, have significantly improved production efficiency, reducing the time and labor required for peptide manufacturing.
• Microbial and Cell-Free Synthesis: Using engineered microbial systems (e.g., bacteria or yeast) or cell-free synthesis technologies can lower the cost of peptide production, particularly for high-volume manufacturing. These systems can often be more scalable and cost-effective than traditional chemical synthesis methods.
• Flow Chemistry: Continuous flow-based synthesis techniques enable scalable, faster, and more efficient peptide production, cutting down on both time and costs compared to batch synthesis methods.
• Outsourcing and Contract Manufacturing: Partnering with specialized contract manufacturing organizations (CMOs) that focus on peptide production can help reduce the capital and operational expenses of in-house production, making large-scale peptide manufacturing more affordable.
• Streamlined Production Systems: Optimizing production systems, such as using improved E. coli strains or mammalian cell lines, can yield higher peptide quantities at lower costs, making the manufacturing process more economical.

Peptides are small but mighty molecules with diverse functions and promising therapeutic applications. While they face challenges in terms of stability and delivery, advancements in peptide synthesis and peptide manufacturing are making it possible to overcome these obstacles. As the field continues to grow, peptide-based drugs are likely to play an even greater role in treating a wide range of diseases in the future.

For more insights into peptide synthesis and manufacturing, visit our comprehensive resources to learn how these small molecules are shaping the future of healthcare.