Deamidation and oxidation in stored peptides
The two reactions behind most slow peptide degradation: the chemistry, which sequences are vulnerable, what accelerates them and how to slow them.
Two chemical reactions account for most of the slow degradation of research peptides in storage: deamidation of asparagine and glutamine, and oxidation of methionine, cysteine, tryptophan and histidine. Neither is visible. Both change the mass by an amount a COA would catch and the activity by an amount an assay might. This note explains the chemistry, which sequences are vulnerable, what accelerates each reaction, and how to slow them down. All Alphex products are for laboratory and in-vitro research only.
Deamidation
What happens. The side-chain amide of asparagine (and more slowly glutamine) attacks the backbone, forming a cyclic succinimide intermediate that hydrolyses to a mixture of aspartate and isoaspartate (the latter with the backbone rerouted through the side chain). The peptide gains about 0.98 Da and acquires a negative charge; the isoaspartate form can alter conformation and activity considerably.
What accelerates it. Alkaline pH (fast above pH 8, slow around pH 4-6), heat, and the residue that follows: Asn-Gly is by far the fastest motif, then Asn-Ser, Asn-His; Asn followed by a bulky residue is slow. Gln deamidates roughly an order of magnitude more slowly than Asn.
In the catalogue. TB-500 (Ac-LKKTETQ) has a C-terminal glutamine; slow, but measurable over months in solution. BPC-157 has no Asn or Gln. GLP-3 (RT), as a glucagon-family peptide, contains glutamine residues and is stored accordingly. Ipamorelin and GHK-Cu have neither.
Oxidation
What happens. Dissolved oxygen, trace metals and light drive oxidation of susceptible side chains. Methionine to methionine sulfoxide (+16 Da) is the most common; tryptophan to oxindolylalanine and kynurenine (+16, +4); cysteine to disulfide-linked dimers or sulfonic acid; histidine, particularly when metal-coordinated, to 2-oxo-histidine. Each adds mass and, usually, polarity, so oxidised forms elute slightly earlier on reverse-phase HPLC.
What accelerates it. Light (see light-sensitive peptides), dissolved oxygen (solutions left open, repeated air exposure), trace transition metals in water or buffer, peroxide contaminants in some polymer surfactants and PEGs, and heat.
In the catalogue. BPC-157 and TB-500 contain no Met, Cys or Trp and are comparatively robust. GHK-Cu's histidine-copper centre is redox-active and light-sensitive; keep dark. Ipamorelin has histidine and aromatic residues; keep solutions dark. GLP-3 (RT) has tryptophan and tyrosine in the backbone; keep dark and cold in solution.
Slowing both
- Stay lyophilised until use; neither reaction runs meaningfully in dry powder at -20 C. See long-term storage.
- Cold and dark in solution: 2-8 C for weeks, -20 C aliquots for longer.
- pH. Do not go more alkaline than solubility requires; deamidation is fastest above pH 8. Mildly acidic to neutral is generally the stability optimum for the catalogue peptides, with the caveat that lipidated peptides may need pH 7.4-8 to dissolve. See buffers for reconstitution.
- Limit air exposure. Cap tubes, do not leave solutions open, do not bubble or shake. Degassed buffer helps for very sensitive work.
- Clean water and reagents. Purified water, analytical-grade salts, no metal contamination; a chelator such as EDTA can protect Met- and Trp-containing peptides, but never for GHK-Cu.
- Aliquot, so each portion is exposed once. See aliquoting.
Detecting them
Both produce new, slightly earlier HPLC peaks and characteristic mass shifts (+1 for deamidation, +16 per oxygen). Assay drift with no visible change is the bench-level sign. See recognising peptide degradation and common peptide impurities.
Alphex research peptides are supplied for laboratory and in-vitro research by qualified researchers only. They are not authorised for human or veterinary use.
Research use only. Alphex products are supplied exclusively for laboratory and in-vitro research by qualified researchers. They are not authorised for human or veterinary use, and nothing in this note is advice on any such use.
Published 25 May 2026. Alphex reviews research notes when the testing method, the catalogue or UK guidance changes.