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Mechano Growth Factor MGF is a splice variant of the IGF gene which increases stem cell count in the muscle and allows for muscle fibers to fuse and mature. This is a process required for growth of adult muscle. Natural MGF is made locally and does not travel into the bloodstream. Synthetic MGF is water based and when administered intramuscularly, travels into the bloodstream. MGF is only stable in the blood stream for only a few minutes. PEGylation is the act of attaching a Polyethylene glycol (PEG) structure to another larger molecule (in this case, MGF). The PEG acts as a protective coating and the theory here is that this will allow the MGF to be carried through the blood stream without being broken down. PEG MGF Background I have to be honest here, and say that in my estimation, PEGylating MGF is basically something a research chemical company did to have a bit of a market with no competition for awhile. That’s not to say that it’s not a decent product, but honestly, in this particular case, I feel that marketing was in the drivers seat with the development of this version of MGF, and science was in the backseat asking “are we there yet?”. Mechano Growth Factor Action MGF is produced biologically when muscle fibers are broken down through resistance (weight training). It is a potent factor in muscle growth. MGF stimulates muscle growth, creates new muscle fibers, promotes nitrogen retention and increases protein synthesis. This compound is commonly used for overall growth of muscle and to promote growth in body parts that are not up to par with the rest of the user’s physique. Results usually depend on dosage. Fat loss and strength increases are not typically seen with MGF’s use (as they are in IGF-1 use). The PEG itself is safe for use as it is approved by the US Food and Drug Administration (FDA) and does not react in the body. The PEG MGF is not broken down in the body and excreted (intact) through urine or feces. Any risk associated PEGylated drugs is due to drug itself not the PEG per se. PEG MGF Technical Data In a study on older rodents, muscle fiber reduction in their older muscles was found to be attributed to decreased activity of satellite cells. After a certain size was reached, growth ceased. In the presence of MGF, satellite cells became activated and hypertrophy in mature muscles continued. In experiments where MGF was administered intramuscularly, there was a 20% increase in the weight of the injected muscle fibers within 2 weeks. In further studies, it took 4 months for IGF to cause a 25% increase in muscle mass. MGF was found to be more potent than IGF-1Ea in rapid muscle growth (4). Note: This data is on “regular” MGF, not the Pegylated version….we can assume similar results, however So, along with regular MGF and Lr3IGF-1, if I felt it to be necessary, I might throw in some PEGMGF on off-days from training, to get additional growth (and again, if it were me, I’d probably recommend 400-500mcg of PEGMGF on off days, with a regular dose of 200mcg of regular MGF + 100mgs of Lr3IGF-1 on training days, -------------------------------------------------------------------------------------------- PEG-MGF, or PEGylated Mechano Growth Factor is a new and innovative form of MGF that outperforms natural MGF many times over. MGF is a splice variant of the IGF gene which increases stem cell count in the muscle and allows for muscle fibers to fuse and mature. This is a process required for growth of adult muscle. Natural MGF is made locally and does not travel into the bloodstream. Synthetic MGF is water based and when administered intramuscularly, travels into the bloodstream. MGF is only stable in the blood stream for only a few minutes. PEGylation is the act of attaching a Polyethylene glycol (PEG) structure to another larger molecule (in this case, MGF). The PEG acts as a protective coating and the theory here is that this will allow the MGF to be carried through the blood stream without being broken down. MGF exhibits local effects in skeletal muscle and without cannot travel through the body without modification. The problem with synthetic MGF is that it is introduced intramuscularly and is water based so it goes into the blood stream. When used this way, MGF only remains stable in the blood stream for a few minutes. Biologically produced MGF is made locally and does not enter the bloodstream. It is also short acting so stability is not an issue. By PEGylating the MGF it is almost as efficient as local produced MGF when used intramuscularly. This is accomplished by surrounding part of the peptide with a structure of polyethylene glycol, which can be attached to a protein molecule. The polyethylene glycol groups protect the peptide but don’t surround it completely. The active sites of the peptide are still free to do their biological function. In this case the shell is a negative charged shield against positively charged compounds that would affect the protein. Neurological research has shown that utilizing PEGylated MGF resulted in a longer more stable acting version of the MGF peptide in serum/blood. ------------------------------------------------------------------------------------------------ -------------------------------------------------------------------------------- PEGylated Mechano Growth Factor is a new and innovative form of MGF that outperforms natural MGF many times over. PEGylation technology was introduced into the pharmaceutical industry more recently to virtually eliminate the problems associated with biopharmaceuticals. Biopharmaceuticals have a lot of negative issues associated with them that make their use limited in the pharmaceutical industry, such as extremely short half-lives caused by proteolytic degradation (often not exceeding 2 minutes), increased renal (kidney) excretion, and inactivation of the peptide caused by your body’s natural immune response. This problem, however, is corrected by attaching different PEG molecules to proteins and peptides. PEG stands for polyethylene glycol, a unique polymer that is non-ionic and soluble in water. By covalently bonding a PEG chain to a peptide you can expand the physical radius of the overall molecule, which creates a “shield” around the peptide and prevents proteases and antibodies from cleaving it and rendering it inactive. PEGylation also has various lengths (weights) and using a chain that is too large can block the binding of the peptide to its receptor. This, and the fact that MGF is a smaller peptide, is why we decided to use a smaller PEG chain and since d-arg MGF is insoluble in water the addition of a PEG chain is a positive feature to this peptide. This prevents the need for acidic solutions and provides a virtually painless injection. Our PEG MGF is also unique in the sense that we did not go with a PEG molecule attached to a normal human MGF peptide. Instead, we decided to use a more stable form of the peptide, a variant with 2 d-arg substitutions at positions 14 and 15, where there was once the natural l-arg. These additions create a more stable peptide in itself, since basic l--arg-l-arg bonds are easily cleaved by proteases in the blood. By creating a d-arg-d-arg bond, instead, we eliminate this problem and extend the half life well beyond basic hMGF. Our PEG MGF also contains another unique addition to its structure. By looking at the difference between hMGF and our PEG MGF, one of the first things you will notice is the addition of an NH2 group at the C-terminal (right) side of the peptide. This amine addition is often used by pharmaceutical companies to, once again, increase the half life of the peptide by making it less susceptible to carboxypeptidases in plasma, which are enzymes that remove amine (NH2) groups from the end of peptides and render them inactive. Since all peptides have a Carboxyl (COOH) and amine (NH2) group attached to the ends of them, the addition of another amine group to the end of the carboxyl side of the peptide greatly decreases the chances of the functional amine group getting cleaved by enzymes. In most cases this addition has no effect on the peptide’s interaction with its receptor. What does all of this science-talk do for you? Greater stability of the MGF peptide, less susceptibility of cleavage from various enzymes, decreased immune response, and decreased excretion rate in the kidneys, all of which greatly increase the half-life of the peptide. hMGF has a half life of less than 20 minutes in the body, but with various technologies that we have added we can extend this half life from minutes to days! Commentary highlighted in green is to further explain the statements from the article and key points from the article are highlighted in red....... The FASEB Journal express article 10.1096/fj.05-3786fje. Published online September 6, 2005 A strong neuroprotective effect of the autonomous Cterminal peptide of IGF-1 Ec (MGF) in brain ischemia Joanna Dłużniewska,* Anna Sarnowska,† Małgorzata Beręsewicz,* Ian Johnson,‡Surjit K. S. Srai,§ Bala Ramesh,§ Geoffrey Goldspink,|| Dariusz C. Górecki,¶ and Barbara Zabłocka* Peptide synthesis The 24 amino acid peptide amide (NH2-YQPPSTNKNTKSQ(d)R(d)RKGSTFEEHK-NH2 corresponding to the shorter consensus mammalian sequence for the C-terminal MGF peptide was synthesized using the Fmoc protection strategy. The D-form of arginine was used for the synthesis instead of the naturally occurring L-form. The N terminus was modified by a PEG derivative (O’O-bis(2-aminopropyl)polyethylene glycol 1900) (Jeffamine) via a succinic acid bridge................. Comments: Goldspink is the scientist that actually discovered MGF and for purposes specific to this study he uses MGF but instead of the human sequence which contains 3 arginines, they use the shorter consensus mamalian sequence containing 2 arginines. They removed the arginine at the 23rd position. Human form MGF has a third arginine at the 23rd position. They are also using the D-form of arginine to keep them from cleaving and makes it more stable. Based on these analyses and taking into account the high degree of homology, we have generated a consensus sequence for the mammalian 24aa C-terminal peptides of the IGF-1 splice variant IGF-1Eb/Ec or MGF (Fig. 1B). This consensus sequence was used to prepare a synthetic, 24 amino acid long MGF C-terminal peptide. Based on the human sequence, this peptide contained two rather than three arginines (Fig. 1B). To increase the stability of the MGF peptide, which was found to be rapidly degraded in the serum or tissue fluids (Yang and Goldspink, unpublished), the D-form of arginine was used for synthesis instead of the naturally occurring Lform. Moreover, the N terminus of the peptide was PEGylated................... Comments: As you can see proof here that plain MGF is not stable and must be PEGylated to stabilize.....from the mouth of Goldspink himself. Such a small and biologically active molecule is a good candidate for development into a therapeutic modality. Indeed, we have shown here that C-terminal MGF peptide can be modified into a more stable and potentially targetable moiety by specific chemical modifications. In contrast, the recombinant full-length IGF-1, although neuroprotective in vitro, was found ineffective when delivered by intracarotid injection. It remains to be elucidated whether this disparity was due to different biological activities or resulted from the increased stability of the modified C-terminal MGF molecule. The difference in permeability through the blood-brain (BBB) barrier could also be a factor, but it has to be stressed that the PEGylated C-terminal MGF and recombinant IGF-1 have similar molecular size. We demonstrate here the efficacy of the modified C-terminal MGF peptide administered as a single bolus injection intra-arterially. This suggests that the stabilized, pegylated peptide molecule was able to cross the BBB and penetrate into the neurones………………….. Comments: As you can see clearly in red that PEGylation made the MGF peptide more stable and more targetable for development of a therapeutic modality for the pharmaceutical world. *Molecular Biology Unit and †Department of NeuroRepair, Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland; ‡Department of Anatomy, §Department of Biochemistry and Molecular Biology, and ||Molecular Tissue Repair Unit, Department of Surgery, Royal Free and University College Medical School, London, England; ¶Institute of Biomedical and Biomolecular Sciences, School of Pharmacy and Biomedical Sciences, University of Portsmouth, England Geoffrey Goldspink, Dariusz C. Górecki, and Barbara Zabłocka are senior coauthors. -------------------------------------------------------------------------------------------- Questions and Answers... i just started the 2mg peg mgf vial. I've heard there isn't any difference between pegylated and normal mgf. I got peg mgf because there wasn't a big difference in price. I've heard about peg-HGH and they say it's great but it's very expensive. Can anyone confirm that peg-HGH is so superior to HGH? I am very interested to it. I am using right now peg mgf at 400mcg (200mcg+200mcg) the night before training day, on the muscle group i target in training the next day. 20minutes after training i use IGF I Lr3 (40+40mcg on the each muscle i shot peg mgf the day before). I'll do this for 4 weeks. I've done igf before so i'll check how good peg mgf does in combination. I'll keep you posted. p.s. i've reconstituted with 2ml BW. ------------------------------------------------------------------------------------------------ i have used both versions of MGF and found as long as you inject the MGF straight after training then it is better than pMGF although pMGF is not a waste(depending on what you are expecting)... The body has to cleeve off the Peg before it can use the MGF so why would you want to do this extra step?? just so you can jab it less often?? it is correct that you would use pMGF the night before you trained that specific bodypart normal dosing is 250-500mcg's once or twice a week with pMGF but i pointed out i find slightly better results from injecting straight after training with MGF then 20min later with IGF-1LR3... BL - Bac water is fine for mixing mate... ----------------------------------------------------------------------------------------------I am just getting ready to finish up 9 weeks of PEG MGF. I used a few different doses, but basically in the 1.25-1.5 mgs per week, and a couple different dosage schedules, Mon- Fri, and Mon- Wed- Fri. When I do it again I will go 500 mcg Mon, Wed, and Fri, as this seemed the most effective. As far as results go, I had excellent recomp, lost fat, hardened up, vascularity up, excellent as far as that went. Nice pumps in the gym, no hypo feeling. Dropped weight, strength wise did ok, basically maintenance. I really liked the peptide, and thought it worked well as far as short term recomp gains. -------------------------------------------------------------------------------------