| Customization: | Available |
|---|---|
| CAS No.: | Research Use Only |
| Formula: | Research Use Only |
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P21 is a small peptide derivative of CNTF. Small molecule mimetics can exert some or all of the effects of larger neutrophic molecules without the side effects mentioned above. P21 was developed through a process called epitope mapping, which uses antibodies to identify target binding sites. In the case of P21, antibodies against CNTF receptor active sites were used to first identify the CNTF binding site. They were then used to confirm which small, synthetic peptides mimicked CNTF binding and thus interfered with antibody binding. The result was the production of P21, which not only binds to the CNTF receptor, but also crosses the blood-brain barrier and placental/lactational barriers. P21 is a tetra-peptide derived from the most active region of CNTF (amino acid residues 148-151). Admantylated glycine was added to the C-terminal end to increase blood-brain barrier permeability and decrease degradation by exopeptidases.
Natural CNTF is too large to cross the blood-brain barrier, has poor plasma stability, an unfavorable pharmacologic profile, and actually promotes the development of anti CNTF-antibodies when administered systemically. Direct administration to the cerebrospinal fluid, while an option, is generally avoided due to pain, risk of infection, and other adverse effects. Unlike full CNTF, P21 has better than 95% stability in artificial gastric juice over 30 minutes, long enough for it to pass through the stomach in most cases. It is roughly 100% stable in the intestine over two hours, which is long enough for it to be absorbed. It is stable in blood plasma for more than 3 hours.
P21 has several effects in the central nervous system, but its primary impact is in the dentate gyrus where it acts to enhance neurogenesis and neuron maturation in the granular cell layer and sub-granular zone. The dentate gyrus, which is part of the hippocampal formation in the temporal lobe of the brain, is thought to contribute to the formation of new episodic memories and the spontaneous exploration/learning that occurs in new environments. The dentate gyrus also plays an important role in pre-processing of information and pattern separation. In essence, pattern separation is what allows mammals to differentiate one memory from another. The dentate gyrus is also of great interest to neuroscientists because it is one of a few brain regions known to have significant rates of neurogenesis in adults.
Research in mouse models shows that P21 does not bind to the CNTF receptor, suggesting that even though it is referred to as a mimetic, it should be clear that P21 is not and analogue of CNTF It appears, rather that P21 acts to inhibit antibodies or other molecules that neutralize CNTF. Thus, though P21 does not directly mimic the effects of P21, it increases the concentration of this most potent of neurogenesis promoters and thus effectively mimics its effects.
Research in mice shows that P21 increases levels of BrdU positive cells in the dentate gyrus. BrdU is a synthetic nucleoside (analogue of thymidine) used to detect proliferating cells in living tissues. In this experiment, it is found concentrated in the dentate gyrus of mice administered P21 but not in the DG of control mice, suggesting that P21 promotes proliferation of cells in this region. To determine if the cells are neurons or not, the expression of NeuN can be measured as it is a marker for mature neurons. It is also significantly increased in mice administered P21 and in the region of BrdU increase, supporting the idea that the increased proliferation is in fact increased neurogenesis.
| Product Name | P21 |
| CAS NO. | N/a |
| Appearance | White freeze-dried powder |
| Purity | 98% HPLC |
| Application | Research peptides |
| Shelf Life | 24 Months |
| Storage | Store at a temperature of 2-8 degrees, protected from light. |
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