[Study of the relationship between analgesic activity and structure of synthetic melanocortin analogs].
Ivanova. D M DM; Vilenskiĭ. D A DA; Levitskaia. N G NG; Andreeva. L A LA; Alfeeva. L Iu LIu; Kamenskiĭ. A A AA; Miasoedov. N F NF
Key Findings
- The analgesic (pain‑relieving) effect of semax depends on the amino‑acid at position 1.
- Replacing methionine with lysine or adding a glucuronic‑acid moiety preserves pain relief; replacing it with glycine eliminates it.
- Removing N‑terminal residues (truncations) abolishes the analgesic activity.
Practical Outcomes
- For DIY biohackers, this suggests that the standard semax formulation may have modest pain‑relieving properties, but only if the peptide’s N‑terminal structure is intact. Modifying semax’s first residue could tweak its effects, though any human use would still be experimental and requires careful dosing and safety assessment.
Summary
In rats, the brain‑active peptide semax (MEHFPGP) reduces pain, but only when its first amino‑acid is the original methionine, a lysine, or when a glucuronic‑acid group is attached to methionine. Cutting off the first few building blocks or swapping methionine for glycine makes the peptide lose its pain‑killing effect.
Abstract
Melanocortins, peptides of the family of adrenocorticotropic (ACTH) and melanocyte-stimulating (MSH) hormones, have a wide range of physiological activity. Heptapeptide semax (MEHFPGP) is an analog of the ACTH4-10 fragment. Previously, pronounced nootropic and neuroprotective activities were shown for this peptide; in addition, it decreases pain sensitivity in animals. In this work, the relationship between analgesic activity of the peptide and its structure was studied. The following analogs of the N-terminal ACTH fragments were used: rMEHFPGP, where r is glucuronic acid, KEHFPGP, GEHFPGP, EHFPGP, HFPGP, and ERP. The peptides were administered intraperitoneally at doses of 0.015, 0.05 and 0.5 mg/kg. Rat pain sensitivity was assessed using the paw-withdrawal test. Truncations of the N-terminal residues eliminated the analgesic activity. The peptide analgesic effect was observed after the replacement of the N-terminal methionine with lysine or after the attachment of glucuronic acid to the methionine, while the peptide with glycine instead of the methionine had no effect on pain sensitivity. Hence, the amino acid at position 1 of semax analogs plays a key role in mediating the analgesic effects of the peptides.
Study Information
pubmed
2006