Key findings
- Tritium-labelled peptide bound cell membranes isolated from rat basal forebrain in a time dependent, specific and reversible way, and the reported binding required calcium ions. [1]
- In artificial phospholipid membrane models the peptide prevented formation of the amyloid beta copper complex and reduced fiber formation in spectrofluorometric and calorimetric assays. [2]
- RNA sequencing of rat cortex and striatum after transient middle cerebral artery occlusion found the peptide shifted hundreds of ischemia disturbed transcripts back toward the unoccluded profile, with the larger gene set in cortex. [3][4]
- In isolated rat brain plasma membranes the peptide changed tritiated GABA binding differently at the high affinity and low affinity sites, and the authors separated that direct membrane effect from a delayed effect measured in a whole-animal restraint stress model. [5]
Identity and structure
- Sequence
- Met-Glu-His-Phe-Pro-Gly-Pro [1]
- Origin
- Analogue of the N-terminal 4-10 fragment of adrenocorticotropic hormone carrying a C-terminal Pro-Gly-Pro tripeptide [1][6]
- Reported binding constants
- Dissociation constant 2.4 nM and a maximum binding capacity of 33.5 fmol per mg protein in rat basal forebrain membranes [1]
- Form as supplied
- Sterile lyophilized powder
Mechanism as studied
The binding work places a specific, calcium dependent recognition site for the heptapeptide in membranes isolated from rat basal forebrain, and the same paper measured a rise in brain-derived neurotrophic factor protein in that region but not in cerebellum. The authors connect the two observations rather than demonstrating a single receptor. [1]
A separate line of work examines the peptide as a copper binding molecule. In artificial membrane models it interfered with the amyloid beta copper complex and with the fibrillogenesis that follows, which is a chemical interaction measured outside any cell. [2]
In rat occlusion models the reported changes are transcriptional and post-translational rather than receptor level. Sequencing found differentially expressed immune and neurosignaling genes, and protein profiling found active CREB raised in subcortical tissue with MMP-9, c-Fos and active JNK lowered in the adjacent cortex. [7][3]
Research findings
Ex vivo
- System
- Cell membranes isolated from rat basal forebrain, and basal forebrain and cerebellum tissue from rats exposed to the peptide
- Measured
- Binding of tritium-labelled peptide over time, its reversibility, its calcium requirement, the dissociation constant and maximum binding capacity, and brain-derived neurotrophic factor protein by sandwich immunoenzymatic analysis
- Reported
- Binding was time dependent, specific and reversible, required calcium ions, and gave a dissociation constant of 2.4 nM with a maximum binding capacity of 33.5 fmol per mg protein. Brain-derived neurotrophic factor protein rose in basal forebrain at 3 h and did not rise in cerebellum. [1]
In vitro
- System
- Artificial phospholipid membrane models with amyloid beta protein and copper ions, plus a cell viability assay
- Measured
- Formation of the amyloid beta copper complex, fibrillogenesis and aggregation by spectrofluorometric and calorimetric assays, and viability by MTT
- Reported
- The peptide prevented formation of the amyloid beta copper complex and showed anti-aggregating activity, and the authors attribute the reduced fiber formation to interference with fibrillogenesis of the complex rather than of free amyloid beta. [2]
Ex vivo
- System
- Isolated plasma membranes from rat brain cells, and a rat acute restraint stress model, testing this peptide alongside the related ACTH(6-9)PGP, ACTH(7-10)PGP and Pro-Gly-Pro-Leu molecules rather than this peptide alone
- Measured
- Binding of tritiated GABA at its high affinity and low affinity specific sites, directly in isolated membranes and in a rat acute restraint stress model
- Reported
- Each peptide altered tritiated GABA binding in its own pattern across the two site classes. Acute restraint stress lowered binding at the low affinity site and left the high affinity site unchanged, and prior peptide exposure did not alter that stress effect. [5]
Preclinical in vivo
- System
- Rat transient middle cerebral artery occlusion model, dorsolateral frontal cortex sampled 4.5 h after occlusion, with the related ACTH(6-9)PGP peptide studied in parallel
- Measured
- Genome wide differentially expressed genes by RNA sequencing, and their grouping into immune and neurosignaling categories
- Reported
- The authors counted 131 differentially expressed genes associated with this peptide and 322 with the related peptide, and reported that both partly prevented the ischemia driven change in immune and neurosignaling expression profiles, with different gene sets for the two structures. [3]
Preclinical in vivo
- System
- Striatum of the same rat transient middle cerebral artery occlusion animals whose frontal cortex was reported earlier, again alongside the related ACTH(6-9)PGP peptide
- Measured
- Differentially expressed genes by RNA sequencing at 24 h, their functional grouping and the overlap between the two tissues
- Reported
- Both peptides produced fewer differentially expressed genes in striatum than in frontal cortex and tended to normalize hundreds of ischemia disturbed transcripts there. Under the related peptide 152 striatal genes, mostly inflammation associated, moved further from the unoccluded profile, and about a hundred genes overlapped between peptides and tissues and mapped to neuroactive ligand receptor interaction. [4]
Preclinical in vivo
- System
- Rat transient middle cerebral artery occlusion model, subcortical structures including the ischemic focus and the adjacent frontoparietal cortex, sampled 24 h after occlusion
- Measured
- Brain expression of MMP-9, c-Fos, JNK and active CREB protein, and construction of a regulatory network from the measured set
- Reported
- Active CREB was raised in the subcortical structures, MMP-9 and c-Fos were lowered in the adjacent frontoparietal cortex, and active JNK was lowered in both tissues. [7]
Handling for in-vitro work
- Assay condition in cited work
- Binding of the labelled peptide to isolated membranes required calcium ions in the assay buffer [1]
- Storage
- Lyophilized at -20 °C, dark and dry; reconstituted aliquots kept cold and used promptly
Open questions
- The cited work identifies a specific binding site in rat basal forebrain membranes but does not name the receptor protein that carries it.
- Whether the artificial membrane aggregation result holds in a cellular amyloid model has not been established in the cited work.
- The transcriptome papers report gene set changes in rat occlusion models; how those transcript counts relate to any measured function in another experimental system is not addressed.
- Evidence for this peptide alone does not characterize a mixture that also contains Selank.
A clinical literature on this sequence exists and concerns finished formulations; it is out of scope for a research material profile.
Lot records
Check the record for the exact material you order. A published paper and a batch certificate answer different questions.
- RV-24-0005-2 ↗Semax · 99.50% HPLC2026-09-16
- RV-24-0005-1 ↗Semax · 99.50% HPLC2026-09-16
References
- Dolotov OV, Karpenko EA, Seredenina TS, et al. Semax, an analogue of adrenocorticotropin (4-10), binds specifically and increases levels of brain-derived neurotrophic factor protein in rat basal forebrain. Journal of neurochemistry. 2006.
- Sciacca MFM, Naletova I, Giuffrida ML, et al. Semax, a Synthetic Regulatory Peptide, Affects Copper-Induced Abeta Aggregation and Amyloid Formation in Artificial Membrane Models. ACS chemical neuroscience. 2022.
- Filippenkov IB, Remizova JA, Stavchansky VV, et al. Synthetic Adrenocorticotropic Peptides Modulate the Expression Pattern of Immune Genes in Rat Brain following the Early Post-Stroke Period. Genes. 2023.
- Filippenkov IB, Shpetko YY, Ales DA, et al. Genes That Associated with Action of ACTH-like Peptides with Neuroprotective Potential in Rat Brain Regions with Different Degrees of Ischemic Damage. International journal of molecular sciences. 2025.
- Vyunova TV, Andreeva LA, Shevchenko KV, et al. Synthetic corticotropins and the GABA-receptor system: Direct and delayed effects. Chemical biology & drug design. 2023.
- Stavchansky VV, Filippenkov IB, Remizova JA, et al. Insight into Glyproline Peptides' Activity through the Modulation of the Inflammatory and Neurosignaling Genetic Response Following Cerebral Ischemia-Reperfusion. Genes. 2022.
- Sudarkina OY, Filippenkov IB, Stavchansky VV, et al. Brain Protein Expression Profile Confirms the Protective Effect of the ACTH(4-7)PGP Peptide (Semax) in a Rat Model of Cerebral Ischemia-Reperfusion. International journal of molecular sciences. 2021.
Publication records fetched from PubMed on 2026-09-20. Profile text reviewed 2026-09-20.