N-terminal degradation of ACTH(4-10) and its synthetic analog semax by the rat blood enzymes.
Potaman. V N VN; Alfeeva. L Y LY; Kamensky. A A AA; Levitzkaya. N G NG; Nezavibatko. V N VN
Key Findings
- ~33-50% of peptide degradation in rat serum is due to a bestatin‑sensitive aminopeptidase that removes the N‑terminal Met and Glu
- s activity",
Practical Outcomes
- Semax’s greater stability suggests it may stay active longer in the body, potentially allowing less frequent dosing or lower doses for similar effects. Because the breakdown products are stable, they might also play a role, so the overall effect isn’t just from the intact peptide. If you’re looking to boost stability further, targeting the bestatin‑sensitive aminopeptidase could be a strategy.
Summary
The study shows that in rat blood, the synthetic peptide semax breaks down more slowly than the natural ACTH(4-10) peptide, and a good chunk of the breakdown is caused by a specific enzyme that trims the first two amino acids. The fragments that form are fairly stable and might still have biological effects, meaning the whole mix—not just the original peptide—could matter when you take it.
Abstract
Degradation of a regulatory peptide ACTH(4-10) and its synthetic analog semax in rat blood and serum was studied using high-performance liquid chromatography. About one third to one half of the serum degrading activity could be ascribed to bestatin-sensitive aminopeptidase which cleaved first and second N-terminal residues Met and Glu producing relatively stable intermediates. Comparable areas under the degradation/accumulation curves for intact peptides and intermediates implied that the latter can contribute to effects of intact peptides. Semax turned out to be more stable than ACTH(4-10) against the action of other enzymes that took part in degradation.
Study Information
pubmed
1991
1991-04-30T00:00:00.000Z
10.1016/s0006-291x(05)80247-5