Understanding Peptide Degradation and Stability

Even the highest-purity peptides will degrade over time under improper conditions. Knowing the common degradation mechanisms and how to prevent them is essential for maintaining peptide quality throughout your research.

Major Degradation Pathways

Hydrolysis

Water molecules attack peptide bonds, breaking the chain.

• Accelerated by heat and extreme pH
• Asp-Pro bonds are particularly susceptible
• Results in truncated peptide fragments

Oxidation

Oxygen and reactive species modify susceptible amino acids.

• Methionine → Methionine sulfoxide
• Cysteine → Disulfide bonds or sulfenic acid
• Tryptophan and Tyrosine also vulnerable

Deamidation

Asparagine and Glutamine lose their amide groups.

• Asn-Gly sequences most susceptible
• Accelerated at high pH and temperature
• Creates charge variants (Asp, Glu)

Aggregation

Peptide molecules clump together.

• Often triggered by partial unfolding
• Accelerated by heat and agitation
• May be irreversible

Environmental Factors

Factor	Effect	Protection
Temperature	Accelerates all degradation	Store cold (-20°C or 2-8°C)
Moisture	Enables hydrolysis	Keep lyophilized, use desiccant
Light	Triggers photo-oxidation	Store in dark, amber vials
Oxygen	Causes oxidation	Inert atmosphere, antioxidants
pH	Accelerates hydrolysis/deamidation	Optimal pH 4-7 for most

Lyophilized vs. Reconstituted Stability

Lyophilized (Powder)

• Most stable form
• Years of stability at -20°C
• Months at 2-8°C
• Keep sealed and dry

Reconstituted (Solution)

• Less stable than powder
• 2-4 weeks at 2-8°C typical
• Aliquot for longer storage
• Avoid repeated freeze-thaw

Signs of Degradation

Warning Signs

• Cloudiness or precipitate in solution
• Color change (yellowing, browning)
• Unusual odor
• Gel formation
• Reduced or inconsistent research results

Best Practices for Stability

Store lyophilized peptides at -20°C
Allow vials to equilibrate to room temperature before opening
Reconstitute only what you need immediately
Aliquot reconstituted peptides to avoid freeze-thaw cycles
Protect from light at all times
Document storage conditions and opening dates