1051 replies to this topic

[Beynini-Zikiyim]

So we all thought to get that stuff in May but it will take some more months i guess..

[megatron]

Surely the synthesis has to be done by now?

[Ghenghis Prawn]

If a spot opens up or another group buy for this please count me in.  New member, although I've been reading for quite some time. 

[xks201]

It's not done yet ask N. IIl see if I can get more details.

[xks201]

Also skscientific is credited for getting the structure from the inventor. I did verify the storage conditions with the inventor as well. Special thanks to sk scientific. I have emailed to check the status on the compound

[jabowery]

Also skscientific is credited for getting the structure from the inventor. I did verify the storage conditions with the inventor as well. Special thanks to sk scientific. I have emailed to check the status on the compound

Presumably this is solid phase peptide synthesis.  From wikipedia's page on peptide synthesis:
 

Solid-phase peptide synthesis (SPPS), pioneered by Robert Bruce Merrifield,^%5B1%5D resulted in a paradigm shift within the peptide synthesis community. It is now the accepted method for creating peptides and proteins in the lab in a synthetic manner. SPPS allows the synthesis of natural peptides which are difficult to express in bacteria, the incorporation of unnatural amino acids, peptide/protein backbone modification, and the synthesis of D-proteins, which consist of D-amino acids.
Small solid beads, insoluble yet porous, are treated with functional units ('linkers') on which peptide chains can be built. The peptide will remain covalently attached to the bead until cleaved from it by a reagent such as anhydrous hydrogen fluoride or trifluoroacetic acid. The peptide is thus 'immobilized' on the solid-phase and can be retained during a filtration process, whereas liquid-phase reagents and by-products of synthesis are flushed away.
The general principle of SPPS is one of repeated cycles of coupling-wash-deprotection-wash. The free N-terminal amine of a solid-phase attached peptide is coupled (see below) to a single N-protected amino acid unit. This unit is then deprotected, revealing a new N-terminal amine to which a further amino acid may be attached. The superiority of this technique partially lies in the ability to perform wash cycles after each reaction, removing excess reagent with all of the growing peptide of interest remaining covalently attached to the insoluble resin.
The overwhelmingly important consideration is to generate extremely high yield in each step. For example, if each coupling step were to have 99% yield, a 26-amino acid peptide would be synthesized in 77% final yield (assuming 100% yield in each deprotection); if each step were 95%, it would be synthesized in 25% yield. Thus each amino acid is added in major excess (2~10x) and coupling amino acids together is highly optimized by a series of well-characterized agents.
There are two majorly used forms of SPPS  Fmoc and Boc. Unlike ribosome protein synthesis, solid-phase peptide synthesis proceeds in a C-terminal toN-terminal fashion. The N-termini of amino acid monomers is protected by either of these two groups and added onto a deprotected amino acid chain.
Automated synthesizers are available for both techniques, though many research groups continue to perform SPPS manually.
SPPS is limited by yields, and typically peptides and proteins in the range of 70 amino acids are pushing the limits of synthetic accessibility. Synthetic difficulty also is sequence dependent; typically amyloid peptides and proteins are difficult to make. Longer lengths can be accessed by using native chemical ligation to couple two peptides together with quantitative yields.
Since its introduction over 40 years ago, SPPS has been significantly optimized. First, the resins themselves have been optimized.^%5B2%5D Furthermore, the 'linkers' between the C-terminal amino acid and polystyrene resin have improved attachment and cleavage to the point of mostly quantitative yields.^{%5B3%5D%5B4%5D%5B5%5D}The evolution of side chain protecting groups has limited the frequency of unwanted side reactions. In addition, the evolution of new activating groups on the carboxyl group of the incoming amino acid have improved coupling and decreased epimerization. Finally, the process itself has been optimized. In Merrifield's initial report, the deprotection of the α-amino group resulted in the formation of a peptide-resin salt, which required neutralization with base prior to coupling. The time between neutralization of the amino group and coupling of the next amino acid allowed for aggregation of peptides, primarily through the formation of secondary structures, and adversely affected coupling. The Kent group showed that concomitant neutralization of the α-amino group and coupling of the next amino acid led to improved coupling.^%5B6%5D Each of these improvements has helped SPPS become the robust technique that it is today.

[Amorphous]

Any update on this group buy? It seems awfully long than expected. Hopefully I we can try it out soon.

[foreseason]

Yeah I agree. I've kept my mouth shut and stayed patient but this is becoming a bit ridiculous.

[xks201]

Talked to N. It is a complex synthesis. They are still working on it. I wish I had a better update than that to give but N is doing his best to get them synthesizing it as quickly as possible. The money is safe. There are no worries there. Therefore, as I said before, he has zero to gain at the moment.  . Nothing seems to go perfectly when it comes to things like this. Sorry for the delay but the job is complex. Half of the US companies I contacted couldn't even do the synthesis because it required special methodology they were not equipped for. I will keep you guys posted.

Edited by xks201, 26 June 2014 - 10:20 PM.

[StevesPetRat]

Hmmm I wonder how this drug will feel when you take it... bdnf linked to neuropathic pain
http://www.ncbi.nlm....ubmed/22613083/

[Amorphous]

This is not bdnf and if this compound shows a similar side-effect is an unknown.

[Nattzor]

It's within the same group that desmopressin (or rather vasopressin) which has great memory enhancing potential (short-term atleast). I'd guess it could be great for memory.

Edited by Nattzor, 28 June 2014 - 09:38 AM.

[mikee37]

count me in also

[medicineman]

It's within the same group that desmopressin (or rather vasopressin) which has great memory enhancing potential (short-term atleast). I'd guess it could be great for memory.

It's an angiotensin 4 analog. At least that's what I remember from the paper and the long discussion here.

[Nattzor]

 

It's an angiotensin 4 analog. At least that's what I remember from the paper and the long discussion here.

 

 

That is correct. Vasopressin (and angiotensin 4) works on the AT1-receptor, Dihexa (and angiotensin 4) AT4, so not super related.

 

I would guess that the receptor family holds promise for cognitive enhancement, we've already seen evidence for it (desmopressin and now dihexa).

 

Although I found this:

 

 

Importantly, strain differences in murine responses to angiotensin IV suggest that some individuals may benefit from drugs targeted to the AT₄ receptor whilst others may be refractory.

- http://www.biomedcen...1-2202/9/S2/S15

Worth reading.

 

Haven't read this yet, but could be worth reading too - http://linkinghub.el...043276002000371

[SearchingForAnswers]

Well,

 

Hopefully this won't take too much longer. But since I'm currently taking nsi-189, I suppose it doesn't matter. I wouldn't want to push my luck by using them both simultaneously (or even within a month of one another).

 

Of course, if the NSI-189 works fantastic, I may get it and never take it...

[agora]

Is the confirmed structure and IUPAC name available anywhere? For people who may want more in the future after trying it from this group buy

[Nattzor]

Has anyone calculated the dose and want to share what it is?

[SearchingForAnswers]

I believe that's earlier in the thread.

[Nattzor]

I believe that's earlier in the thread.

 

Already calculated, it's about 20-25 mg.

[taktikz]

Anyone want to give me their spot?

[tolerant]

Can I still participate?

[mandaryn]

What's the status? There seem to be less and less hits on this thread, and I'll admit to being a little concerned. Do we have any new information?

[xks201]

All Nyles says is that they are still working on the synthesis and DHEXA has confirmed it is a difficult synthesis. If by the end of the month there is no solid update I will speak to N about changing suppliers and go from there. I am getting impatient myself. 

[Ben]

Which company is doing the synthesis? How could so many people order knowing nothing about who is making this?

[drg]

Seems to be the way of these things not to know who the manufacturer is.... not that it is a good thing. Probably just nyles7 ppl he uses to make every compound he sells. I don't understand why no one will ever say like.. yadayada, vlk, ect... but nyles has a business to maintain.

[xks201]

Yeah...He won't tell me. Which is fine because I have nothing at risk.

[PWAIN]

Yeah...He won't tell me. Which is fine because I have nothing at risk.

 

I had to laugh at the "ill Informed" vote on this post. Duh, xks201 is saying I don't know, admitting that he is ill informed. Was that done as a joke?

[pro-v]

XKS: What is your contingency plan with everyone's funds if Nyles supplier can't come through?

[xks201]

The Nemo user has been negative repping all my posts. At this point I just ignore it