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The peptide GRKKRRQRRRCDMAEHTERLKANDSLKLSQEYESI is a synthetic bifunctional peptide composed of a TAT-derived cell-penetrating peptide (CPP) domain and a biologically active intracellular sigma peptide (ISP) sequence. This construct is widely used in neuroscience research as a modulator of axonal regeneration and neural repair pathways.
The N-terminal GRKKRRQRRR sequence is derived from the HIV-1 TAT protein and enables efficient cellular uptake across a broad range of cell types, including neurons and glial cells. This CPP domain facilitates intracellular delivery of the peptide, allowing the functional ISP region to access cytoplasmic and membrane-associated targets.
Mechanism of Action: PTPσ and CSPG Signaling Modulation
The C-terminal ISP sequence interacts with protein tyrosine phosphatase sigma (PTPσ), a receptor involved in binding chondroitin sulfate proteoglycans (CSPGs). CSPGs are major inhibitory components of the extracellular matrix that accumulate following central nervous system injury and limit axonal regeneration.
By interfering with PTPσ-mediated signaling, this peptide disrupts the inhibitory effects of CSPGs, thereby promoting neurite outgrowth, axonal extension, and neural plasticity. This mechanism has been extensively studied in models of spinal cord injury, traumatic brain injury, and neurodegenerative conditions.
Applications in Neuroscience and Regenerative Medicine
- Axonal regeneration and neurite outgrowth studies
- Spinal cord injury and central nervous system repair research
- Neuroplasticity and synaptic remodeling investigations
- In vitro and in vivo models of neural regeneration
- Modulation of extracellular matrix inhibition (CSPG signaling)
Role of the TAT Cell-Penetrating Peptide (CPP)
The TAT domain enables efficient intracellular delivery of the ISP sequence without the need for transfection reagents. This property allows direct application of the peptide in cell culture and animal models, making it a convenient tool for studying intracellular signaling pathways and therapeutic mechanisms.
For additional CPP-based delivery systems, see related cell-penetrating peptides and polyarginine (R9) peptides.
Advantages of TAT-ISP Peptide
- Efficient intracellular delivery via TAT CPP domain
- Targeted modulation of PTPσ signaling pathway
- Promotes axonal regeneration and neural repair
- Widely used in CNS injury and neuroregeneration research
- Compatible with in vitro and in vivo experimental systems
Molecular Features
TAT CPP domain (GRKKRRQRRR)
Provides rapid cellular uptake and enables intracellular delivery of bioactive peptides.
ISP functional domain
Targets PTPσ receptor interactions and disrupts CSPG-mediated inhibition of neuronal growth.
Neuroregenerative activity
Supports neurite extension and axonal regeneration in inhibitory extracellular environments.
Related Products:
Polyarginine (R9) peptide
Cys(Npys)-(Arg)9 peptide
Cell-penetrating peptides (CPPs)
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