Comment · Mon, January 15, 2018
N-arachidonoylsemax: any interest? (cross-post from r/nootropics)
Original post in this thread
theindoleshop · 7 points
Hey guys, stumbled across an article on this interesting compound. It's a prodrug for semax itself, just as N-acetylsemax is. The prodrug group is similar to that found in anandamide, N-arachidonoyldopamine, N-arachidonoylserotonin, VDM13, AM-404, et cetera. It is likely to be hydrolysed into semax/active peptide fragments via FAAH (fatty acid amide hydrolase).
I found this article which mentions its hydrolytic stability. It is vastly more stable than semax and also appears to have superior binding affinity. From the article:
The loss of arachidonoyl-Semax was 20% after 50-min incubation with rat brain membranes, and the level of this hydrolytic cleavage was only slightly decreased in the presence of a series of protease inhibitors (Fig. 2). The unmodified Semax was hydrolyzed by 47% for 30 min under these conditions.
*AA-MEHFPGP was twofold better bound than Semax to still unidentified specific binding sites of this peptide in rat cerebellum membranes (KA 104 and 51 nM, respectively). The membrane-bound [3 H]AA-MEHFPGP was specifically displaced with unlabeled Semax, whereas the membrane-bound tritium labeled Semax was displace…
What they were answering
Direct reply to the original post — see the thread post above.
u/MisterYouAreSoDumb
You got my PM last week, right? We synthesized AA-Semax a few years ago. The issue is scaling and cost. When our lab synthesizes the arachidonic acid, the solid phase peptide synth works. However, it's VERY expensive to do that way. When we get bulk AA made for us, then try to use that, the solid phase peptide synth fails. We tried a bunch of things, but could not figure out how to scale it up efficiently. I was going to circle back around to it at some point, but our card processing and banking issues kind of put a stop to me dumping a bunch of money into R&D of peptides.
If we could figure out how to do it effectively, for a reasonable cost, I would love to do it. We've worked on a lot of things in the background that are successful in small batches, but fail to scale up appropriately. Just for reference, the cost per vial was a few hundred dollars when we made the arachidonic acid internally. So not economically feasible. If we could get larger batches of arachidonic acid synthed cheaper, and still have it work in the solid phase peptide synth, then we could get that number down.