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Mechano Growth Factor

Ok guys, I need an opinion from someone who knows their biology! I want to invest in some mgf to run along with my igf. I recently discovered that there are a lot of companies online that will synthesize custom peptides for you, all you have to do is provide the amino acid sequence and any post translational modifications if you so choose to have any. Knowing the amino acid sequence from mgf (Tyr-Gln-Pro-Pro-Ser-Thr-Asn-Lys-Asn-Thr -Lys-Ser-Gln-Arg-Arg-Lys-Gly-Ser-Thr-Phe-Glu-Glu-Arg-Lys-NH2)it would be more economical to have them make it and buy it from them. If I did take this route, would I be getting the same mgf peptide I would get if I bought from a reputable peptide company?

There are millions of millions of ways of folding even the shorter polypeptides and no way to emulate correct folding in vivo without using cellular organells and knowing which peptid you want to achieve.

No luck for you here, sry.

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I’ve never seen it that cheap. Do you have any way of doing purity analysis?

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[quote]bushidobadboy wrote:
I get 2000mg of MGF for $22.

So no, it would not be cheaper or even feasible to get a biotech company to make it for you.

BBB[/quote]
2000mg! How much are you using?

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We are all actually talking about MICROgrams here, right?

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[quote]PederLustzo wrote:
There are millions of millions of ways of folding even the shorter polypeptides and no way to emulate correct folding in vivo without using cellular organells and knowing which peptid you want to achieve.

No luck for you here, sry.[/quote]

This is not really in the right context. A peptide like MGF does not need a special folding procedure. Whether it is going to provide a significant physiological effect, regardless of the preparation/formulation procedure, is another important issue though.

[quote]bushidobadboy wrote:
it would not be cheaper or even feasible to get a biotech company to make it for you.
[/quote]

It would probably be more expensive but feasible sure, and if we are talking something that is a bit complex to synthesize (MGF is not) then it could be a better route, pending the “biotech” and “competing” companies though. A lot of the online vendors I’d almost say are pretty much biotech anyways…

I don’t really know if I have seen any good reports for MGF results though. I’ve read some reports where people are taking MGF plus so many other things that it is hard to say if their results are due to it or other things. Have you seen anything definitive BBB?

[quote]Rusty Barbell wrote:

[quote]PederLustzo wrote:
There are millions of millions of ways of folding even the shorter polypeptides and no way to emulate correct folding in vivo without using cellular organells and knowing which peptid you want to achieve.

No luck for you here, sry.[/quote]

This is not really in the right context. A peptide like MGF does not need a special folding procedure. Whether it is going to provide a significant physiological effect, regardless of the preparation/formulation procedure, is another important issue though.

[/quote]

So are you saying that the primary structure will correctly fold into the native structure 100% of the time? That was not my understanding of protein folding; but I am not an expert in that area.

Well each peptide/protein is a case by case basis. I can try to generalize it as simply as I can though. It is a bit hard to use MGF as an example because it is still relatively unknown how it works. It probably binds to DNA because it has lots of positive charge, but in what shape it is not known, although I would guess probably an alpha helix.

The fact is shorter peptides (short with respect to a large protein) are flexible and as such if you simply put them in an environment where they are close to their target (lets say inside a muscle cell for MGF), they will be fully capable of finding their way there and acting on it. Generally for a peptide when they are just floating around in a cell they are in a semi-correct conformation and although it might not be 100% as it would look when it is bound to DNA (or whatever its target is), it is close enough to where the amount of energy it needs to go from the “floating around” state to the “active” state is very small and incapable of altering the biological process in significant amounts.

Nature does a magnificent job in designing these sorts of things to work very well with as little energy input as possible.

Moving to bigger proteins, nearly all of them cannot function properly without folding in the ER. Cell surface proteins like receptors are a good example. They have complex mechanical functions necessary to permit them to bind a ligand and induce signal, and this requires them to be folded properly. Receptors are generally 500-1000 amino acids in length and they might not just have 1 alpha helix like MGF, but 10 alpha helices, 10 beta sheets and 10 loops with disulfide bonds and hydrophobic and electrostatic interactions needed to hold them all together. This doesn’t just happen. You can’t just toss a 750 amino acid receptor into solution and expect it to be able to work like the much smaller MGF can. It has to be folded first (there are protein machines that do this).

And to answer your question, sometimes this process can mess up. There are a few protein folding disorders where an amino acid mutation screws up the folding process for a protein in a person and because of this it will get stuck in the ER during folding and degraded because the cell recognizes this and does not let it out (instead tagging it for destruction) and hence you have some sort of disorder (some deadly). These are pretty uncommon, but do exist. The actual rates at which a healthy person would have a protein misfold and subsequently destroyed should be very small, although I am not sure if anyone has really studied this in good detail because it is a technically challenging question to investigate. I cannot remember seeing much of anything. However if I had to make a general guess, given how good Nature is at its jobs… I don’t know, maybe 1 in 10,000 is misfolded on average and subsequently degraded? Who knows though maybe more maybe less. This is all a very active field of research.

Insulin is another good example to blur the lines a bit. Insulin is 51 amino acids total cut into 2 separate chains connected by 2 disulfide bonds and one of the chains has 1 additional disulfide within itself. You can’t just take insulin’s 2 chains, or the linear insulin precursor and inject it and expect it to work. It has to be folded in the ER with the proper disulfide configuration and then enzymatically processed to create the 2 separate chains (still connected by the disulfides) that are the biologically active form. This form however, like MGF, can be administered by a person and assuming it can get near a functional target, is fully capable of readily eliciting its biological action.

[quote]Rusty Barbell wrote:
Well each peptide/protein is a case by case basis. I can try to generalize it as simply as I can though. It is a bit hard to use MGF as an example because it is still relatively unknown how it works. It probably binds to DNA because it has lots of positive charge, but in what shape it is not known, although I would guess probably an alpha helix.

The fact is shorter peptides (short with respect to a large protein) are flexible and as such if you simply put them in an environment where they are close to their target (lets say inside a muscle cell for MGF), they will be fully capable of finding their way there and acting on it. Generally for a peptide when they are just floating around in a cell they are in a semi-correct conformation and although it might not be 100% as it would look when it is bound to DNA (or whatever its target is), it is close enough to where the amount of energy it needs to go from the “floating around” state to the “active” state is very small and incapable of altering the biological process in significant amounts.

Nature does a magnificent job in designing these sorts of things to work very well with as little energy input as possible.
[/quote]
Thanks for that in-depth answer. I have studied enough on proteins that I pretty much knew the the part below, but the smaller peptide formation is relatively knew to me. So small peptides dont generally need some molecular chaperone to assist in folding? Does the type of secondary structure indicate ease of folding in any way? I only asked because you mentioned that MGF was probably an alpha helice instead of a beta sheet. It would still have to form some supersecondary or tertiary structure to be active right?

Thanks a lot for the explanation!

DLB

Yea so pretty much anything that is <50 amino acids and has no disulfide bonds is going to be able to automatically form the needed conformation in the presence of its receptor/target. There might be a few exceptions but nothing I am really aware of.

Generally the intrinsic properties of the amino acids themselves will dictate the peptide to form at least a partially-active conformation all the time, as nature doesn’t want it just to be in any (wrong) conformation when it is needed. Some amino acids highly prefer a helix (Ala and Glu especially) whereas others prefer beta sheet (Thr, Leu, Val especially) and others a random/flexible conformation (Gly). This was all taken into account when this stuff was designed. :stuck_out_tongue_winking_eye:

For example a helical peptide like glucagon. Glucagon is 29 amino acids and when it activates the receptor amino acids 6-29 are a helix while 1-5 are some sort of extended strand structure (this is all known to be true), but in solution glucagon, when there are no receptors nearby, is generally not the ideal helix from 6-29 it needs to be to activate the receptor. It may be partially helical or even really close to the exact structure it should be, but not exactly there most the time. This goes back to peptides having lots of freedom in solution to move around and sample difference conformational states, which also permits them to be able to sample so many conformations so quickly that they have little trouble finding the right one they need to be in to activate their receptor.

Whatever MGF does and in whatever conformation (I predict helix based on its amino acids) it likely does the same sort of thing.

/hijack

Thats great stuff, RB, thanks! Love when I can learn something new = )