N-Acetyl-Semax

N-Acetyl-Semax is Semax, the ACTH(4-7)-Pro-Gly-Pro heptapeptide, with its N-terminal amino group acetylated. That single change alters how the peptide binds copper(II), and researchers have compared the two forms directly in neuroblastoma cells. Most route-of-delivery work, including brain uptake after intranasal application and breakdown by nasal mucus enzymes, was carried out with unmodified Semax. Research Market supplies this N-Acetyl-Semax spray in solution in a spray bottle, with a lot-specific certificate of analysis, for laboratories working with nasal-route research models. It is sold strictly for laboratory research use.

Chemical structure and identification

• Parent peptide: Semax, CAS 80714-61-0, PubChem CID 9811102
• Parent sequence: Met-Glu-His-Phe-Pro-Gly-Pro (MEHFPGP)
• Modification: Acetylation of the N-terminal amino group (Ac-Semax)
• Form: Supplied in solution in a spray bottle
• Analytical methods: RP-HPLC for purity and mass spectrometry for identity, reported on the batch certificate of analysis

Research applications

• Effect of N-terminal acetylation: Acetylation changed the main Cu(II) complex of Semax from a CuN₄ to a distorted CuN₃O chromophore; unlike Semax, Ac-Semax did not protect SH-SY5Y neuroblastoma cells from Cu(II) toxicity, while Zn(II) binding and cellular Zn(II) influx were comparable [1]
• Intranasal brain uptake (parent peptide): With tritium-labeled Semax given intranasally to rats, 0.093% of the administered radioactivity per gram was found in brain at 2 minutes, 80% of it as intact peptide, with Pro-Gly-Pro the main metabolite [2]
• Breakdown by nasal mucus enzymes: Semax and the glyprolines Pro-Gly-Pro-Leu, Pro-Gly-Pro-Gly and Pro-Gly-Pro were exposed to leucine aminopeptidase and to enzymes from nasal mucus, brain membranes and rat blood; the glyprolines were considerably more stable, and Semax was cleaved to His-Phe-Pro-Gly-Pro [3]
• Route comparison: In rats, intranasal Semax improved passive avoidance learning more than intraperitoneal Semax, but changed pain sensitivity in the Randall-Selitto test only by the intraperitoneal route [4]
• Ischemia-reperfusion transcriptome: RNA-Seq of rat brain 24 hours after transient middle cerebral artery occlusion found 394 genes differentially expressed with Semax versus saline, with inflammation-related genes suppressed and neurotransmission-related genes activated [5]

Reference citations

1. Magrì A. et al. (2016). Influence of the N-terminus acetylation of Semax, a synthetic analog of ACTH(4-10), on copper(II) and zinc(II) coordination and biological properties. J Inorg Biochem, 164:59–69. PMID 27586814 · DOI
2. Shevchenko K.V. et al. (2006). [Kinetics of Semax penetration into the brain and blood of rats after its intranasal administration]. Bioorg Khim, 32(1):64–70. PMID 16523722 · DOI
3. Shevchenko K.V. et al. (2013). [Proteolysis of simple glyprolines by leucine aminopeptidase and enzymes from nasal slime, brain membranes, and rat blood]. Bioorg Khim, 39(3):320–325. PMID 24397030 · DOI
4. Manchenko D.M. et al. (2010). [Nootropic and analgesic effects of Semax following different routes of administration]. Ross Fiziol Zh Im I M Sechenova, 96(10):1014–1023. PMID 21268834
5. Filippenkov I.B. et al. (2020). Novel insights into the protective properties of ACTH(4-7)PGP (Semax) peptide at the transcriptome level following cerebral ischaemia-reperfusion in rats. Genes (Basel), 11(6):681. PMID 32580520 · DOI

Parent-compound data from PubChem CID 9811102 (Semax). Literature summaries describe published preclinical research and are not claims about this product’s effects in humans or animals.