NA Smax

Research Overview

N-Acetyl Semax Amidate serves as a valuable research tool for investigating enhanced cognitive mechanisms, sustained neuroprotective pathways, and prolonged neuroplasticity modulation in laboratory settings. This modified heptapeptide represents an optimized analog of Semax (ACTH 4-10 analog), incorporating N-terminal acetylation and C-terminal amidation to dramatically extend metabolic stability and duration of biological activity.

The peptide’s development addressed the enzymatic degradation that limits unmodified peptide activity. Semax itself was developed as a metabolically stable fragment of ACTH (adrenocorticotropic hormone), and NA-Semax further enhances this stability through terminal modifications. The N-terminal acetyl group blocks aminopeptidase degradation, while C-terminal amidation prevents carboxypeptidase attack, resulting in extended plasma half-life and sustained tissue effects.

NA-Semax research demonstrates potent effects on cognitive function, neuroplasticity markers, neuroprotection, and neurotransmitter systems with substantially extended duration compared to unmodified Semax. Laboratory studies investigate its effects on learning and memory consolidation, BDNF expression, neuronal survival under stress conditions, and modulation of dopaminergic, serotonergic, and cholinergic systems in preclinical models.

Molecular Characteristics

Complete Specifications:

• CAS Registry Number: 80714-61-0 (Semax base structure)
• Molecular Weight: 813.93 Da
• Molecular Formula: C₃₇H₅₁N₉O₁₀S
• Amino Acid Sequence: Ac-Met-Glu-His-Phe-Pro-Gly-Pro-NH₂
• Peptide Classification: Modified ACTH(4-10) analog
• Modifications: N-terminal acetylation, C-terminal amidation
• Appearance: White to off-white lyophilized powder
• Solubility: Water, bacteriostatic water, phosphate buffered saline
• Contains: Methionine (oxidation-sensitive)

The peptide’s modified structure retains the core ACTH(4-10) sequence (Met-Glu-His-Phe-Pro-Gly-Pro) with terminal modifications that dramatically enhance stability. The sequence includes methionine at position 1, which requires protection from oxidation during storage and handling. Two proline residues (positions 5 and 7) contribute to conformational stability. The aromatic phenylalanine and histidine residues are important for melanocortin receptor interactions. Terminal acetylation and amidation create a more lipophilic molecule with enhanced blood-brain barrier penetration.

Pharmacokinetic Profile in Research Models

NA-Semax pharmacokinetic characterization in preclinical research reveals substantially enhanced properties:

Enhanced Stability Profile:

• Plasma half-life: Approximately 180-240 minutes (vs. 15-20 minutes for Semax)
• Enzymatic resistance: 8-12 fold increased stability vs. unmodified peptide
• Brain tissue persistence: Extended CNS detection and activity
• Biological activity duration: Effects observed for 8-16 hours post-administration

Absorption and Distribution:

• Multiple administration routes: intranasal (preferred), subcutaneous, intraperitoneal
• Blood-brain barrier penetration: Efficient CNS access
• Brain regional distribution: Hippocampus, cortex, striatum
• Cerebrospinal fluid levels: Sustained concentrations vs. plasma

Metabolic Considerations:

• Primary degradation: Slower internal peptide bond cleavage
• Methionine oxidation: Potential oxidative modification under stress
• Metabolites: Extended formation time vs. unmodified Semax
• Excretion: Primarily renal following gradual metabolism

These enhanced pharmacokinetic properties enable research protocols investigating sustained cognitive enhancement, prolonged neuroprotection, and cumulative neuroplastic effects with simplified dosing schedules.

Research Applications

Sustained Cognitive Enhancement Research

NA-Semax serves as a research tool for investigating prolonged cognitive enhancement mechanisms:

• Extended Memory Consolidation: Investigation of long-term memory formation and strengthening
• Sustained Attention Research: Analysis of prolonged attentional focus and vigilance
• Multi-Day Learning Protocols: Examination of cumulative learning effects across extended training
• Working Memory Studies: Research on sustained working memory capacity improvements
• Cognitive Flexibility: Investigation of enhanced task-switching and mental adaptability

Research protocols employ multi-day cognitive testing batteries, chronic dosing paradigms, and longitudinal assessment of cognitive performance markers including spatial navigation, object recognition, fear conditioning, and operant learning tasks.

Prolonged Neuroprotection Studies

Laboratory studies investigate NA-Semax in sustained neuroprotective research:

• Chronic Oxidative Stress: Examination of long-term protection against ROS and oxidative damage
• Excitotoxicity Models: Research on sustained protection against glutamate-mediated toxicity
• Ischemic Injury: Investigation of extended neuroprotection in stroke and hypoxia models
• Neurodegenerative Models: Studies in chronic progressive neurodegeneration paradigms
• Mitochondrial Protection: Research on sustained mitochondrial function preservation

Experimental models include chronic oxidative stress exposure, repeated ischemic insults, neurotoxin-induced degeneration, and genetic neurodegenerative models where extended protection provides experimental advantages.

Extended Neuroplasticity Investigation

Research applications focus on sustained neuroplasticity mechanism analysis:

• BDNF Expression Studies: Investigation of prolonged brain-derived neurotrophic factor upregulation
• Synaptic Density Research: Analysis of cumulative effects on synapse formation and maintenance
• Long-Term Potentiation: Studies on sustained enhancement of synaptic strengthening
• Dendritic Remodeling: Research on structural plasticity changes with chronic exposure
• Neurogenesis Studies: Investigation of sustained effects on neural progenitor proliferation

Laboratory protocols examine NA-Semax effects through molecular analysis (Western blot, qPCR), electrophysiological recordings (LTP, LTD), and structural analysis (dendritic spine counts, synaptic markers) over extended timeframes.

Melanocortin Receptor Research

NA-Semax provides a research tool for investigating sustained melanocortin receptor activation:

• MC4 Receptor Studies: Investigation of melanocortin-4 receptor activation and downstream signaling
• Receptor Desensitization: Analysis of chronic agonist exposure effects on receptor function
• cAMP Pathway Research: Studies on sustained cyclic AMP signaling and PKA activation
• Gene Expression Analysis: Investigation of melanocortin-responsive gene transcription
• Brain Region-Specific Effects: Research on differential melanocortin system effects across CNS regions

Research protocols investigate NA-Semax effects through receptor binding assays, second messenger quantification, gene expression profiling, and region-specific pharmacology.

Neurotransmitter System Modulation

Laboratory investigations examine NA-Semax effects on multiple neurotransmitter systems:

• Dopaminergic System: Research on sustained dopamine release, metabolism, and receptor expression
• Serotonergic Modulation: Studies on extended serotonin system effects and mood regulation
• Cholinergic Enhancement: Investigation of sustained acetylcholine system function
• Glutamatergic Effects: Analysis of prolonged excitatory neurotransmission modulation
• Noradrenergic Activity: Research on extended norepinephrine system effects

Neurotransmitter research employs microdialysis, HPLC analysis, receptor autoradiography, and behavioral pharmacology to characterize NA-Semax’s extended effects on neurotransmitter systems.

Laboratory Handling and Storage Protocols

Lyophilized Powder Storage:

• Store at -20°C to -80°C in original sealed vial
• Protect from light, moisture, and oxidation
• Desiccated storage environment required
• Nitrogen or argon atmosphere recommended for long-term storage
• Stability data available for 12+ months at -20°C

Reconstitution Guidelines:

• Reconstitute with sterile water, bacteriostatic water (0.9% benzyl alcohol), or appropriate buffer
• Deaerated solvents preferred to minimize methionine oxidation
• Add solvent slowly down vial side to minimize foaming
• Gentle swirling motion recommended (avoid vigorous shaking)
• Allow complete dissolution before use (typically 1-2 minutes)
• Final pH should be 6.0-7.0 for optimal stability

Reconstituted Solution Storage:

• Short-term storage: 4°C for up to 14 days (extended vs. Semax)
• Long-term storage: -20°C in aliquots to avoid freeze-thaw cycles
• Protect from light and oxidative conditions
• Antioxidants (ascorbic acid) may be added to prevent methionine oxidation
• Single-use aliquots recommended to maintain peptide integrity
• Avoid repeated freeze-thaw cycles (maximum 3-4 cycles)

Oxidation Prevention:
NA-Semax contains methionine which is susceptible to oxidation. Store under inert atmosphere when possible and minimize exposure to air during handling. Reconstituted solutions should be used promptly or stored under nitrogen headspace.

Quality Assurance and Analytical Testing

Each NA-Semax batch undergoes comprehensive analytical characterization:

Purity Analysis:

• High-Performance Liquid Chromatography (HPLC): ≥98% purity
• Analytical method: Reversed-phase HPLC with UV detection at 214nm and 280nm
• Oxidation product monitoring: Verification of methionine integrity

Structural Verification:

• Electrospray Ionization Mass Spectrometry (ESI-MS): Confirms molecular weight 813.93 Da
• Amino acid analysis: Verifies sequence composition
• Terminal modification confirmation: Validates acetylation and amidation
• Peptide content determination: Quantifies actual peptide content by weight

Contaminant Testing:

• Bacterial endotoxin: <5 EU/mg (LAL method)
• Heavy metals: Below detection limits per USP standards
• Residual solvents: TFA and acetonitrile within acceptable limits
• Water content: Karl Fischer titration (<8%)
• Oxidation products: Monitored and within specifications

Documentation:

• Certificate of Analysis (COA) provided with each batch
• Third-party analytical verification available upon request
• Stability data documented for recommended storage conditions
• Batch-specific QC results traceable by lot number

Research Considerations

Experimental Design Factors:

Researchers should consider several factors when designing NA-Semax experiments:

1. Extended Activity Profile: NA-Semax’s prolonged duration enables once-daily or less frequent administration, simplifying chronic study protocols.

2. Administration Route: Intranasal administration shows excellent bioavailability and direct nose-to-brain transport in research models. Consider route selection based on research questions.

3. Concentration Selection: Enhanced potency and duration may require lower concentrations than unmodified Semax. Establish dose-response relationships.

4. Temporal Dynamics: Design measurement timelines to capture extended effects. Assessment at 4, 8, 12, and 24 hours reveals sustained activity patterns.

5. Oxidation Control: Methionine content requires attention to oxidative stress during experiments. Control oxidative conditions in experimental protocols.

6. Comparative Studies: Direct comparison with unmodified Semax illuminates specific advantages of terminal modifications and extended stability.

Mechanism Investigation:

NA-Semax’s mechanisms involve multiple pathways:

• Melanocortin receptor (MC4R) activation
• BDNF upregulation via TrkB signaling
• Neurotransmitter system modulation (dopamine, serotonin, acetylcholine)
• Antioxidant enzyme expression
• Anti-apoptotic signaling pathway activation
• NGF and other neurotrophic factor expression

Extended stability allows investigation of cumulative and long-term mechanistic effects.

Compliance and Safety Information

Regulatory Status:
N-Acetyl Semax Amidate is provided as a research chemical for in-vitro laboratory studies and preclinical research only. This product has not been approved by the FDA for human therapeutic use, dietary supplementation, or medical applications.

Intended Use:

• In-vitro cell culture studies
• In-vivo preclinical research in approved animal models
• Laboratory investigation of biological mechanisms
• Academic and institutional research applications

NOT Intended For:

• Human consumption or administration
• Therapeutic treatment or diagnosis
• Dietary supplementation
• Veterinary therapeutic applications without appropriate oversight

Safety Protocols:
Researchers should follow standard laboratory safety practices when handling NA-Semax:

• Use appropriate personal protective equipment (lab coat, gloves, safety glasses)
• Handle in well-ventilated areas or fume hood
• Follow institutional biosafety guidelines
• Minimize oxidative exposure during handling
• Dispose of waste according to local regulations for biological/chemical waste
• Consult material safety data sheet (MSDS) for additional safety information

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