ProtoKinetix' anti-aging glycopeptide, trademarked AAGP™ is a small (580.96 Daltons), stable, synthetic replicas of the larger (>2,600 Daltons), less stable AFGP which has been found to have protective properties in nature. The small size of AAGP™ enables it to penetrate cells and allows it to pass through both cell and capillary junctions in vivo. In addition, its bioactivity at a variety of pHs (5.3-10.3) and temperatures (-196°C to 22°C) and efficiency at concentrations (1mg/ml) is well below its toxic dose (50mg/ml), making it a candidate to enter into the next stages of translational research.
AAGP™ has a chemical formula of C20H35CIF2N4O11, solubility in water of 650g.l-1, and is also soluble in methanol, ethanol and DMSO. The optimal concentration is 1-10mg/ml, depending on cell line and stress test. The optimal is pH: 5.3 - 7.3, depending on cell line and stress test.
AAGP™ has gone through a series of tests in various outsourced laboratories in Europe and North America. These tests have proven its ability to protect a multitude of cell lines (Hela cells, adult fibroblast, neonatal fibroblasts, human neuronal stem cells, mouse neuronal stem cells, mouse islet cells, blood platelets, CD34+ cells, and keratinocytes) against UVA, UVC, Hydrogen Peroxide, Inflammatory (ILβ), Time, Temperature (-196°C, -80°C, -3°C, 3°C, 4°C, 15°C and 22°C) and Low Serum induced cell death at pHs from 5.3 -10.5.
The average increase in cell survival credited to AAGP™ in the face of these conditions was over 55%. This cannot be attributed to AAGP™ increasing cell proliferation as it had been found that AAGP™ has no affect on cell doubling times in either Hela or fibroblast cells.
In addition to protecting cell survival AAGP™ also preserves cell functionality. This has been tested via stem cell markers, CD34+ functionality tests, and in vivo studies where AAGP™ treated transplanted islet cells were found to reduce blood glucose concentrations in diabetic mice by 40% by day 40 in comparison to islet cells which were transplanted into mice without first being exposed to AAGP™.
MECHANISM OF ACTION
The mechanism of action of AAGP™ is now under study. However, its ability to protect against inflammation- induced cell death in exposure to hydrogen peroxide, UVA, and UVC suggests a role for AAGP™ in the inflammation pathway. In addition, when exposed to an inflammatory mediator, interleukin β (ILβ), the presence of AAGP™ reduced COX-2 expression three fold. Inflammation plays a major role in many pathological conditions suggesting AAGP™ may not just be usable in cell and organ storage but also in pharmacological treatments.
The full results of these extensive tests can be found in the 'Test Results & Protocols' section of the website.
ANTIFREEZE GLYCOPROTEINS (AFGPs) TO ANTI-AGING GLYCOPEPTIDES (AAGPs™)
AFGPs have proven useful in many applications. However, they are limited by their cost (approximately $10,000/gram), instability, and size (2,600 - 24,000 Daltons). Their large size restricts their use in medicine as they are unable to pass through capillaries into interstitial tissue and are unable to reach target cells. Molecules must be less than 600 Daltons to diffuse through the capillaries. In addition, molecules must be less than 1000 Daltons to pass through cell junctions into neighbouring cells and less than 600 Daltons to cross the blood-brain barrier.
With these issues in mind Dr. Geraldine-Castelot-Deliencourt invented AAGP™ to be a smaller, more stable synthetic version of AFGP.