What are peptides used for and what does research say about their therapeutic applications?

Peptides: Therapeutic Applications and Current Research

Peptides are short chains of amino acids with diverse therapeutic applications including growth hormone stimulation, cardiovascular disease management, and potential for treating metabolic disorders, though many applications remain investigational with limited FDA-approved indications.

What Are Peptides?

Peptides are biopolymers consisting of 2-50 amino acids that occupy a unique chemical space between small molecules and larger proteins 1. They can be:

• Linear chains or cycles with post-translational modifications
• Produced by cellular ribosomal machinery or non-ribosomal enzymes
• Naturally occurring as signaling molecules, hormones, or defense compounds
• Synthetically created for therapeutic purposes

FDA-Approved Therapeutic Applications

Currently, the most well-documented FDA-approved peptide therapeutic is tesamorelin (EGRIFTA SV), which:

• Functions as a growth hormone-releasing factor (GRF) analog 2
• Binds to GRF receptors to stimulate synthesis and release of endogenous growth hormone 2
• Acts on target cells including chondrocytes, osteoblasts, myocytes, hepatocytes, and adipocytes 2
• Has specific approved indications for HIV-associated lipodystrophy 2

Natriuretic Peptides in Cardiovascular Applications

Natriuretic peptides represent one of the most well-studied peptide classes with established clinical utility:

• BNP and NT-proBNP serve as powerful diagnostic tools for heart failure with high sensitivity (90%) and specificity (70%) 3
• For BNP, levels <100 ng/L rule out heart failure, while levels >500 ng/L strongly suggest it 3
• NT-proBNP requires age-specific cutoffs: 450 ng/L for <50 years, 900 ng/L for 50-75 years, 1800 ng/L for >75 years 3
• These peptides predict morbidity and mortality in heart failure, acute coronary syndromes, and ICU patients 4
• A decrease of >30% during heart failure treatment indicates good prognosis 4

Emerging Therapeutic Applications

The peptide therapeutics field is rapidly expanding:

• Approximately 140 peptide therapeutics were in clinical trials as of 2015 5
• More than 80 peptide-based drugs have reached market for conditions including diabetes, cardiovascular diseases, and urological disorders 6
• Current research focuses on multifunctional peptides, cell-penetrating peptides, and peptide drug conjugates 5
• Peptides show promise for treating conditions resistant to conventional therapies 3

Advantages of Peptide Therapeutics

Peptides offer several advantages as therapeutic agents:

• High selectivity and efficacy with relatively good safety profiles 5
• Ability to interfere with protein-protein interactions crucial in biological processes 7
• Potential to cross membranes or reach intracellular targets 7
• Unique biological functions that can hardly be mimicked by other chemical substances 7

Limitations and Considerations

Despite their promise, peptides face several challenges:

1. Limited bioavailability: Tesamorelin has less than 4% bioavailability after subcutaneous administration 2
2. Short half-life: Tesamorelin has a mean elimination half-life of only 8 minutes 2
3. Special handling requirements: Many peptides require specific storage conditions and administration routes
4. Potential for immunogenicity: Some peptides may trigger immune responses
5. Cost considerations: Production and purification can be expensive

Clinical Applications Beyond Cardiovascular Disease

Peptides are being investigated for numerous applications:

• Metabolic disorders: Several peptides target diabetes and obesity
• Dermatology: Peptides boost skin health in cosmetic applications 6
• Oncology: Peptides can target specific cancer cells or pathways
• Infectious diseases: Antimicrobial peptides show promise against resistant pathogens
• Neurology: Neuropeptides may address neurological disorders

Optimal Peptide Characteristics

For clinical and research applications, optimal peptides typically have:

• Length of 6-25 amino acids 3
• Fully tryptic structure without missed cleavage sites 3
• Avoidance of methionine, asparagine, and glutamine (prone to modification) 3
• Carbamidomethylation of cysteine-containing peptides to prevent oxidation 3

Conclusion

Peptides represent a growing class of therapeutics with applications spanning multiple medical disciplines. While their full potential is still being explored, they offer unique advantages in targeting specific biological pathways with high selectivity. Current FDA-approved applications remain limited, but ongoing research suggests peptides will play an increasingly important role in future therapeutic strategies.