Bulk Nutrition Forums -> CJC-1295 with modification

Agent8

Posted: Jul 2 2009, 11:14 PM

Your enemy is ignorance and ego!!!

Group: Advanced Members
Posts: 357
Member No.: 158873
Joined: 30-August 07

How does this look? A rough draft for bussiness web site. go directly to the last paragraph! Any Suggestions?

PEG Mechano Growth Factor (IGF-1 Ec)

Sequence: 1 2mg/vial $75.00 (less expensive & easy to make)

Sequence: 2 2mg/vial $95.00 (more difficult and expensive to make)

* Sequences listed at bottom

• Loss of muscle mass in old age and in certain diseases is associated with an impaired ability to express MGF.
• The ability to produce MGF declines with age, and this is commensurate with the decline in circulating GH levels.
• MGF has been shown to boost muscle mass by improving the ability of waste tissue to grow.
• MGF has been shown to improve the ability of wasted tissue growth.
• MGF has been shown to activate muscle stem cells.
• MGF has been shown to increase the upregulation of protein synthesis.
• MGF induces rapid muscle hypertrophy
• MGF has considerable potential as a genetic means of treating muscle cachexia.
• Mechano Growth Factor (MGF) targets skeletal tissue, and promotes muscle growth by repairing the damaged tissue and upregulating protein synthesis.

The sale of PEG Mechano Growth Faactor (IGF-1 Ec) is not intended for use in the diagnosis, cure, mitigation, treatment, or prevention of any disease, or to affect the structure or any function of the body of man or other animals. The sale of PEG Mechano Growth Factor (IGF-1 Ec) is restricted to research application is strictly prohibited and not endorsed by Anabolic Peptide Laboratory.

Detailed description:

PEGylation, is a process of attaching the strands of polymer PEG to molecules mostly peptides, proteins, and antibody fragments, that can help to meet the challenges of improving the safety and efficiency of many therapeutics. It produces alterations in the physiochemical properties including changes in conformation, electrostatic binding, hydrophobicity, etc. These physical and chemical changes increase systemic retention of the therapeutic agent. Also, it can influence the binding affinity of the therapeutic moiety to the cell receptors and can alter the absorption and distribution patterns. PEGylation technology is now widely used for the modification of proteins, peptides, antibody fragments, oligonucleotides and the like. Among the advantages of PEGylation technology are the following:

• increases bioavailability
• increases blood circulation of the peptide
• optimizes pharmacokinetics
• decreases immunogenicity, and
• decreases frequency of administration.

PEG in all molecular weights are soluble at concentrations less than a 50:50 w/w concentration in water and other solvents. PEGs require heat to be soluble in toluene, methanol, ethanol, and isopropanol. PEGs are not soluable in ethers, ethylene glycol, hexane, and are not soluble in most alcohols at room temperature. If you need an organic solvent, dichloromethane and acetonitrile are two good choices.
The sequencing of the human genome shows that there are only about 40,000 genes. However, there are many more proteins. This is because some genes are spliced to produce different protein/peptides which usually have different biological functions. Combining physiological and molecular biology methods made it possible to identify and characterize a local muscle growth/repair factor (MGF). After resistance exercise, the IGF-1 gene is spliced toward MGF which ”kick starts” hypertrophy and repair of local muscle damage by activating the muscle stem cell as well as anabolic processes, Interestingly. Loss of muscle mass in old age and in certain diseases is associated with an impaired ability to express MGF.

Mechano Growth Factor (MGF) also known as IGF-1Ec is a growth factor/repair factor that is derived from exercised and damaged muscle tissue. MGF has been shown to boost muscle mass by improving the ability of wasted tissue to grow and improve itself by activating stem cells and increasing upregulation of protein synthesis. MGF is a part of the IGF family, but, in case of MGF, this part of the peptide acts as a separate growth factor involved in initiating muscle satellite (stem) cell activation in addition to its IGF-1 receptor domain which increases protein synthesis, and hence improves muscle mass. (Adams GR 2002).

Mechano Growth Factor MGF) is derived from the insulin-like growth factor (IGF-1) but its sequence differs from the systemic IGF-1 produced by the liver. MGF is expressed by mechanically overloading muscle and is involved in tissue repair and adaptation. It is expressed as a pulse following muscle damage and is apparently involved in the activation of muscle satellite (stem) cells. These donate nuclei to the muscle fibers that are required for repair and for the hypertrophy processes which may have similar regulatory mechanisms. Hence, Mechano Growth Factor (MGF) appears to be more anabolic than IGF because MGF responds to the signals produced by damaged muscle tissue induced by exercise and actually repairs the tissue induced by exercise and actually repairs the tissue and prevents cell death.

Loss of muscle mass (sarcopenia) is one of the main problems associated with aging as it has health care as well as socioeconomic implications. The growth hormone (GH)/IGF-1 axis is regarded as an important regulator of muscle mass. However, it is now appreciated that other tissues in addition to the liver express IGF-1 and that there are local as well as systemic form of IGF-1 which have different functions.

At least two different kinds of IGF-1 that are expressed by skeletal muscle are derived from the IGF-1 gene by alternating splicing, one of which is expressed in response to physical activity which has been called “mechano growth factor” (MGF). The other is similar to the systemic or liver type (IGF-1Ea) and is important as the provider of mature IGF-1 required for upregulating protein synthesis.

MGF differs from systemic IGF-Ea in that it has a different peptide sequence which is responsible for replenishing the satellite (stem) cells in skeletal muscle, in other words it is more anabolic. In vivo experiments in which muscles of the rat were subjected to mechanical damage or injection of myotoxic agent also demonstrated (Hill & Goldspink, 2003) that MGF precedes muscle satellite (stem) cell activation. This is in accord with the finding that when skeletal muscle cells in culture, were either transfected with the MGF cDNA or were treated with the MGF carboxy peptide they increased in number but stayed a monocleated myoblasts (Yang & Goldspink. 2002).

It appears that MGF plays a dual role in including satellite cell activation as well as protein synthesis and this is probably why it is much more potent than the liver type or IGF-1Ea for inducing rapid muscle hypertrophy.

The ability to produce MGF declines with age, and this is commensurate with the decline in circulating GH levels. GH treatment up regulates the level of IGF-1 gene expression in older people and when combined with resistance exercise more is spliced toward MGF and hence should improve the ability of muscle to respond to physical activity. (Goldspink and Harridge 2004).

The characterization of a local tissue repair factor (mechano growth factor, MGF) that is produced by exercised and/or damaged muscle by differential splicing of the IGF-1 gene provides understanding of how muscle is maintained in the young normal individual. Mechano Growth Factor, or MGF, is different to the systemic IGF-1 as it has an insert of 49 base pairs of exon 5 that introduces a reading frame shift resulting in a C terminal peptide with unique properties.

Muscle is a post-mitotic tissue and as cell replacement is not a means of tissue repair there has to be an efficient local repair mechanism otherwise the damaged cells undergo cell death. The extra nuclei for muscle repair and hypertrophy are provided by the muscle satellite (stem) cells. The pool of these stem cells apparently replenished by the action of MGF, which is produced as a pulse following a mechanical challenge. Unfortunately, the production of MGF is deficient in certain diseases such as in the muscular dystrophies in which the mechanotransduction mechanism, which may involve the dystrophin complex, is defective. In elderly muscles, decreased levels of growth hormone apparently mean that there is less primary RNA transcript of the IGF-1 gene to be spliced towards MGF. Consequently, there is an increasing ability to maintain muscle mass during ageing. Delivery of MGF and cDNA or peptide produces marked increases in the strength of normal as well as diseased muscle and, therefore, MGF has considerable potential as a genetic means of treating muscle cachexia. (Goldspink 2006).

Skeletal muscle is one of the few tissues with the capacity with the capacity for rapid and widespread repair. The source of this regenerative ability lies in precursor stem-cell reserves that are harbored by the myofibers. The myofiber (muscle fibers) that compose skeletal muscle are muscle cells packed with contractile machinery (myofibrils), recharge energy sources (mitochondria), many nuclei (myonuclei), and a cytoplasmic unit (sarcoplasm, over two-thirds of which is water), each competing in a sense for space inside the cell. (Linstedt SL 1998). Mechano Growth Factor targets skeletal tissue, and promotes muscle growth by repairing the damaged tissue and upregulating protein synthesis.

PEG MGF is also unique in the sense that it is not a PEG molecule attached to a normal human MGF peptide. Instead, there is 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 (sequence 1) and further more substituting position 23 hist with d-arg (sequence 2) increases its stability even more. The problem is eliminated and extends the half life well beyond basic hMGF. PEG MGF also contains another unique addition to its structure. By looking at the difference between hMGF and 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.

Sequence: 1
PEG-Suc-Tyr-Gln-Pro-Pro-Ser-Thr-Asn-Lys-Asn-Thr-Lys-Ser-Gln-d-Arg-d-Arg-Lys-Gly-Ser-Thr-Phe-Glu-Glu-His-Lys-NH2

Sequence: 2
PEG-Suc-Tyr-Gln-Pro-Pro-Ser-Thr-Asn-Lys-Asn-Thr-Lys-Ser-Gln-d-Arg-d-Arg-Lys-Gly-Ser-Thr-Phe-Glu-Glu-d-Arg-Lys-NH2

SWEEETTTT!!! HoBro's!!!!

Agent8

Posted: Jul 3 2009, 11:48 AM

Your enemy is ignorance and ego!!!

Group: Advanced Members
Posts: 357
Member No.: 158873
Joined: 30-August 07

QUOTE (DownTown @ Jul 3 2009, 10:23 AM)

Just going to let you know, the first sequence is 18 bucks every where ive seen it. the second is 24bucks, so that might not be a big seller for you. you might wanna find a cheaper source if your going to do this buisness idevour.

So your saying seq 1: $9/mg and seq 2: $12/mg?

What about this one. I could beat purepeptides prices if I wanted to!

Drug Affinity Complex-Growth Hormone Releasing Hormone (DAC-GHRH)/CJC-1295 with modification

2mg/vial $55.00

• It increases protein synthesis and stimulates the growth of new muscle tissue.
• Allows for normal growth in short children with GH deficiency.
• Increases muscle mass (and physical strength if combined with moderate exercise).
• Reduces wrinkling of the skin and some other effects of skin aging.
• Re-grows internal organs that have atrophied with age.
• It increases muscle mass through the creation of new muscle cells (which differs from hypertrophy).
• It promotes lipolysis, which results in the reduction of adipose tissue (body fat(.
• Increases bone density.
• Faster recovery from exercise, exertion, and injuries.
• Strengthens the immune system.

The sale of CJC-1295 is NOT intended for the diagnosis, cure, mitigation, treatment, or prevention of any disease, or to affect the structure or any function of the body of man or other animals. The sale of CJC-1295 is restricted to research applications ONLY, any other application is strictly prohibited and not endorsed by Bionix.

Detailed description:

It is important to begin the discussion of CJC-1295 with a discussion of the parent of the Growth Hormone Releasing Factor which is somatocrinin., This peptide ultimately gave birth to the newer generations of Growth-hormone-releasing hormone peptides (CJC-1295).

Growth-hormone-releasing hormone (GHRH), also known as growth-hormone-releasing factor (GRF or GHRH) or somatocrinin, is a 44-amino acid peptide hormone produced in the arcuate nucleus of the hypothalamus. GHRH is released from neurosecretory neve terminals of these arcuate neurons, and is carried by the hypothalamo-hypophysical portal circulation to the anterior pituitary gland where it stimulates growth hormone secretion. GHRH stimulates the production of growth hormone.

GHRH gave birth to a more compact growth hormone releasing factor known as Sermorelin which is a synthetic analogue of growth hormone releasing hormone, which is produced in the hypothalamus. Sermorelin acetate is the acetate salt of an amidated synthetic 29-amino acid peptide that correspondes to the amino-terminal segment of the naturally occurring human growth hormone-releasing hormone (GHRH or GRF) consisting on 44 amino acid residues.

The free based of sermorelin has the empirical formula C 149 H 246 N 44 O 42 S and a molecular weight of 3,358 daltons. Semrmorelin stimulates the secretion of growth hormone by acting directly on the pituitary gland, in the brain. In contrast to GHRH which is a 44 amino acid sequence Sermorelin is a 29 amino acid peptide hormone and is also known as (GRF 1-29 NH2). Sermorelin was sold in the United States with the brand name GEREF by Serono Biotechnologies, which later was sold to Merck, they stopped production of sermorelin in November 2002.

So, what was the problem with Sermorelin, or GHRH for that matter? The clinical use of growth hormone-releasing hormone (GHRH) is limited by its short half-life. Also it follows the Sermorelin faced the same difficulties and thus is limited by its short half life (approximately 12 min. following intravenous injection in humans), mainly due to its susceptibility to rapid enzymatic degradation, Thus, the product quickly dissipated in the body and the peptide could not stay in the body long enough to have medicinal impact. A Munafo, T X Q Nguyen, O Papasouliotis, H Lecuelle, A Preistley and M O Thorner (2005). There were attempts to resolve some of the short half-life issues with Sermorelin, in fact a PEGylated GHRH was developed. Even though PEGylated GHRH solved some of the degradation issues, the much more potent CJC-1295, rendered PEGylated GHRH obsolete.

Instead of using the PEGylated technology, the technology of bioconjugation was employed. In vivo bioconjugation to serum albumin is a useful tool to increase the half-life of small molecules or peptides in plasma. In vivo bioconjugation occurs when a strategically placed reactive group on a bioactive peptide reacts with the nucleophilic entity found in the blood or in sc interstitium to form a stable bond. The foremost nucleophile is the thiol, and its most abundant source in these fluids is Cys34 on albumin. The thiol on Cys34 reacts with a Micheal receptor, such as maleimido derivative, leading to a new bioactive protein construct that will adopt an extended half-life due to stabilization from enzymatic degradation or reduced elimination through the kidney. It therefore became logical to combine the long-lasting effect of bioconjugation with the proper GRF analog. Lucie Jette, Roger Leger, Karen Thibaudeau, Corinne Benquet, Martin Robitaille, Isabelle Pellerin, Veronique Paradis, Pieter van Wyk, Khan Phar and Dominique P Bridon (2005).

CJC-1295 is a synthetic modification of growth hormone releasing factor (GRF) with D-Ala, Gln, Ala, and Leu substitution at positions 2, 8, 15, and 27 respectively. These substitutions create a much more stable peptide with the substitution at position 2 to prevent DPP-IV cleavage, position 8 to reduce asparagine rearrangement or aine hydrolysis to aspartic acid, position 15 to enhance bioactivity, and position 27 to prevent methionine oxidation. By applying the Drug Affinity Complex (DAC) technology to GRF, the peptide selectively and covalently binds it circulating albumin after subcutaneous (sc) administration, thus prolonging its half-life. These substitutions are key in increasing the overall half-life of CJC-1295 but there lies an even greater reason as to why the half-life has been extended from ~7 minutes to greater than 7 days. Bioconjugation takes a reactive group and attaches it to a peptide, which in turn reacts with a nucleophilic (usually a partially negative molecule) entity found in the blood to form a more stable bond. Albumin, one of the most abundant substances I the human body is chosen as the nucelophile by this particular peptide thanks to a cys34 thiol group that attracts it. By combining the tetrasubstituted GHRH analogue with maleimodoproprionic acid using a Lys linker, you creat a GHRH peptide with high binding affinity for albumin.

So how effective is bioconjugation? How long will CJC-1295 stay in ones system? How will CJC-1295 impact IGF-1 levels? This is the exact question researchers asked and a study was conducted to determine the efficacy of CJC-1295. The objective of this study was to examine the pharmacokinetic profile, pharmacodynamic effects, and safety of CJC-1295, a long-acting GHRH analog. The study design was two randomized, placebo-controlled, double-blind, ascending dose trials with durations of 28 and 49 days. Healthy subjects, ages 21-61 years old were studied. After a single injection of CJC-1295, there were dose-dependent increases in mean plasma GH concentrations by 2- to 10-fold for 6 days or more and in mean plasma IGF-1 concentration by 1.5- to 3-fold for 9-11 days. The estimated half-life of CJC-1295 was 5.8-8.1 days. After multiple CJC-1295 doses, mean IGF-1 levels remained above baseline for up to 28 days. No serious adverse reactions were reported. Sam L. Teichman, Ann Neale, Betty Lawence, Catherine Gagnon, Jean-Paul Castaigne and Lawrence A. Frohman (2006). What was the research dose used in the study? A particularly important question, the dosage was 30-60 micrograms per kilogram body weight.

This bears repetition, GH remained elevated for up to six days! IGF-1 concentrations were up 1.5 to 3 fold for 9-11 days! And the estimated half-life of CJC-1295 is 5.8-8.1 days! IGF-1 levels were elevated up to 28 days! At a dosage of 30-60 micrograms per kilogram of body weight, with no significant side effects. Excuse all the emphasis but this is a truly remarkable research product, its ability for efficacy is self-evident.

So in sum, what is CJC-1295? CJC-1295 is a long-acting analog of GH-releasing hormone. CJC-1295 exhibits the same effects of Human Growth Hormone. It has the ability to promote muscle mass, increase bone density, improve protein synthesis, increase IGF-1 levels potently, strengthen immune systems, stimulate the production of bone marrow cells that produce red blood cells, and of course reduce excess body fat, especially abdominal fat. (The reduction of abdominal fat is the single most profound effect of GH replacement.)

Sequence:

Tyr-D-Ala-Asp-Ala-Ile-Phe-Thr-Gln-Ser-Tyr-Arg-Lys-Val-Leu-Ala-Gln-Leu-Ser-Ala-Arg-Lys-Leu-Leu-Gln-Asp-Ile-Leu-Ser-Arg-Lys(Maleimidopropionyl)-NH2

SWEEETTTT!!! HoBro's!!!!