Peptide Stability Predictor
Estimate the half-life category of a peptide based on sequence features, modifications, and degradation susceptibility. Free interactive tool for peptide researchers.
Stability Calculator
Degradation Mechanisms
Deamidation
Asn and Gln residues undergo spontaneous deamidation at neutral pH. Asn-Gly sequences are particularly susceptible (t½ ~1-2 days). The reaction produces Asp/isoAsp, altering charge and potentially disrupting structure.
Oxidation
Met and Cys residues are oxidized by reactive oxygen species. Met → Met sulfoxide is reversible; further oxidation to Met sulfone is irreversible. Trp is also susceptible to oxidation under photooxidative conditions.
Isomerization
Asp residues undergo base-catalyzed isomerization to isoAsp via a succinimide intermediate. This converts L-Asp to L-isoAsp, potentially disrupting secondary structure. The reaction is accelerated by Gly flanking residues.
Proteolysis
Exopeptidases (aminopeptidases, carboxypeptidases) degrade N- and C-termini. Endopeptidases (DPP-4, neprilysin, ACE) cleave internal bonds. Terminal modifications and D-amino acids protect against exopeptidase attack.
Half-Life Categories
| Category | Half-Life | Examples | Stabilization Strategies |
|---|---|---|---|
| Very Short | <1 hour | GLP-1 (native), VIP, oxytocin | PEGylation, fatty acylation, cyclization |
| Short | 1–24 hours | Exenatide, insulin, melanotan II | D-amino acids, terminal modifications, albumin binding |
| Medium | 1–7 days | Liraglutide, dulaglutide, cagrilintide | Fc fusion, fatty acylation, D-amino acid substitutions |
| Long | 1–4 weeks | Semaglutide, tirzepatide, lanreotide | Albumin binding, Fc fusion, depot formulations |
| Very Long | >4 weeks | Insulin degludec, PEGylated peptides, microsphere formulations | Multi-hexamer formation, high MW PEG, depot injections |
Stabilization Strategies
Chemical Modifications
- Terminal acetylation/amidation
- D-amino acid substitution
- Cyclization (head-to-tail, side-chain)
- PEGylation
- Fatty acylation (albumin binding)
Formulation Approaches
- Lyophilization (dry powder)
- Microsphere depot (PLGA)
- Liposomal encapsulation
- Nanoparticle delivery
- Hydrogel formulations
Sequence Design
- Avoid Asn-Gly sequences
- Minimize Met/Cys exposure
- Introduce β-branched residues
- Disulfide bond introduction
- Minimize aggregation-prone regions
Frequently Asked Questions
What is peptide half-life?
Peptide half-life is the time required for 50% of the peptide to degrade under physiological conditions. It depends on degradation mechanisms including enzymatic proteolysis, chemical degradation, and aggregation propensity.
What are susceptible residues?
Susceptible residues are amino acids prone to chemical degradation: Asp (isomerization, deamidation), Met (oxidation), Asn (deamidation), and Gln (deamidation). Their frequency correlates inversely with chemical stability.
How accurate is this predictor?
This tool provides categorical estimates based on empirical rules and published data. Actual half-lives depend on additional factors including secondary structure, solvent accessibility, pH, temperature, and protein binding. For precise values, experimental stability testing is required.
Can this tool predict in vivo stability?
This tool estimates chemical stability under physiological conditions. In vivo half-lives also depend on renal clearance, hepatic metabolism, and receptor-mediated endocytosis, which are not captured in this model.