848 replies to this topic

[onemanatatime]

 

count me in for whatever the minimum will have to be, preferably if its synthes. in the us and quality ensured like mentioned above. Also will have to have some creative labeling - marking. shipping outside US

 

I have a US company ready to make the peptide for us! For those who are outside the US you we will need to come up with packaging and labeling that will allow for an easy pass through customs. I can't be responsible for a package that doesn't make it though. 

 

 

I'd definitely be interested in something like this--can you be a bit more specific on how you're working out the cost/person? I assume there's some economy of scale to factor in.

 

 

Yes the price per mg will be less with a 100mg order than 50mg. 

 

 yeah well if you have a labeling machine, you could basically label it as whatever and that makes it basically easy. Just mark it as say vitamin C powder test for drinking water etc. 

btw whats the shelf life for this stuff ? can you store it in a way wich makes it viable for years ? 

[smithx]

Are you specifying the exact peptide used in the study?

 

FOXO4 D-Retro-Inverso peptide:

H-ltlrkepaseiaqsileaysqngwanrrsggkrppprrrqrrkkrg-OH

 

The researchers had it manufactured by Pepscan, so that company would be the best bet for getting the identical compound. Has anyone contacted them yet for pricing?

 

 

[meatsauce]

Are you specifying the exact peptide used in the study?

 

FOXO4 D-Retro-Inverso peptide:

H-ltlrkepaseiaqsileaysqngwanrrsggkrppprrrqrrkkrg-OH

 

The researchers had it manufactured by Pepscan, so that company would be the best bet for getting the identical compound. Has anyone contacted them yet for pricing?

 

Yes of course.  Its a simple sequence any legit peptide company could make it I'm sure. Someone did contact them its very expensive through them. 

[smithx]

What was Pepscan's price?

 

Did you talk to GenScript yet?

[Andey]

 

 

 For those who are outside the US you we will need to come up with packaging and labeling that will allow for an easy pass through customs. I can't be responsible for a package that doesn't make it though. 

 

 

Shouldnt be a problem. At least in Ukraine peptides goes under a customs radar essentially as a food supplement. Its simply a protein so its kinda true.

[smithx]

For anyone interested, I obtained a quote from GenScript, who are generally very reliable. Lower purities would be much cheaper, but I think 98% is what would be desired.

 

Chemical Peptide Synthesis: FOXO4 D-Retro-Inverso
peptide: Quantity 1000 mg ; Purity: >98%; Length: 46;
Aliquoting To: 200,

 

Sequence:
ltlrkepaseiaqsileaysqngwanrrsggkrppprrrqrrkkrg,

 

[Peptide solubility test] [Guaranteed Hydrochloride]
Guaranteed TFA removal: $798.66

 

Subtotal(United States Dollar) $ 10,611.76 Discount: $ 2,943.93 Total: $ 7,667.83
Estimated Shipping/Handling(United States Dollar) $37.05
Total Quote (United States Dollar) $ 7,704.88
 

So that's $7.70 per mg or $38.53 per 5mg vial.

 

I don't know that I am going to try it yet, before more data is available, but if 5mg is a reasonable starting dose, $38.53 isn't super expensive for that.

 

 

[chris1299]

The original study involved a conjugate of FOXO4-DR1 and the neutralized but still highly reactive HIV-TAT1, (both compunds still needs injecting, by the way...)  The HIV-TAT1 part attaches itself to CD4 immune system cells such as T-cells and macrophages thus inducing cell death in senescent immune cells, and rescuing the aging immune system by depleting senescent immune cells.  On the other hand injecting FOXO4-DR1 has no such rescue capability.

 

The 2017 Baar research article says:

"To facilitate cellular uptake of FOXO4-DRI, it was designed as a fusion with HIV-TAT, a basic and hydrophilic sequence that allows energy-independent cellular uptake of cargo through transient pore formation (Herce and Garcia, 2007). Using an antibody against HIV-TAT, we observed FOXO4-DRI to be taken up as soon as 2–4 hr after administration and to remain detectable for at least 72 hr (Figure 2J). Given that the affinity of antibodies is generally low, this indicates FOXO4-DRI effectively enters senescent cells at high intracellular concentrations, which remain abundant and stable over a prolonged period of time. Following its uptake, FOXO4-DRI reduced the number of senescence-induced FOXO4 foci, PML bodies, and 53BP1 DNA-SCARS while not affecting the number of small 53BP1 foci (Figure 2K)."
No mention of immunosenescence related to use of HV-TAT in that paper, but maybe you're thinking of some other source? Anyway, I'd like more clarification on whether FOXO4 unmodified by HIV-TAT will work in vivo or not before committing to a buy. Can anyone explain this a little more?

Edited by chris1299, 26 June 2017 - 05:37 PM.

[TaiChiKid]

 

The original study involved a conjugate of FOXO4-DR1 and the neutralized but still highly reactive HIV-TAT1, (both compunds still needs injecting, by the way...)  The HIV-TAT1 part attaches itself to CD4 immune system cells such as T-cells and macrophages thus inducing cell death in senescent immune cells, and rescuing the aging immune system by depleting senescent immune cells.  On the other hand injecting FOXO4-DR1 has no such rescue capability.

 

The 2017 Baar research article says:

"To facilitate cellular uptake of FOXO4-DRI, it was designed as a fusion with HIV-TAT, a basic and hydrophilic sequence that allows energy-independent cellular uptake of cargo through transient pore formation (Herce and Garcia, 2007). Using an antibody against HIV-TAT, we observed FOXO4-DRI to be taken up as soon as 2–4 hr after administration and to remain detectable for at least 72 hr (Figure 2J). Given that the affinity of antibodies is generally low, this indicates FOXO4-DRI effectively enters senescent cells at high intracellular concentrations, which remain abundant and stable over a prolonged period of time. Following its uptake, FOXO4-DRI reduced the number of senescence-induced FOXO4 foci, PML bodies, and 53BP1 DNA-SCARS while not affecting the number of small 53BP1 foci (Figure 2K)."
No mention of immunosenescence related to use of HV-TAT in that paper, but maybe you're thinking of some other source? Anyway, I'd like more clarification on whether FOXO4 unmodified by HIV-TAT will work in vivo or not before committing to a buy. Can anyone explain this a little more?

 

 

When I first read about the HIV-TAT approach, I was very impressed.  HIV-TAT allows infiltratiing CD-4 immune cells such as killer T-cells and macrophages which then carry out the actual deletion of senescent cells.  By infiltrating the immune system, the FOXO4-DR1 molecule is inside each CD-4 immune cell, thus enabling body wide clearance.  I honestly am quite cautious that plain old FOXO4-DR1 could have the same bodywide effect.
 

[chris1299]

Here's a link to the 2007 Herce and Garcia paper that is cited in the Baar paper: https://www.ncbi.nlm...les/PMC2565759/. As far as I can tell it doesn't look like the Baar group were using HIV-TAT to selectively infiltrate immune cells, but rather to get FOXO4-DRI into any cell whatsoever. Are you maybe thinking of an HIV-TAT application from a different bit of research? Or can you provide a quote showing that the Baar approach doesn't rely more generally on HIV-TAT for cell infiltration?

I'm not trying to start a fight or nitpicking: as far as I can tell the Baar approach, which is the basis for our collective interest in FOXO4, may use HIV-TAT for general cell infiltration. If so, then we should be figure out how to get the peptide with the HIV-TAT modification, since FOXO4-DRI may be useless without it.

[chris1299]

But also, the FOXO4-DRI peptide that's patented might have the HIV-TAT modification already--if so, no worries.

[TaiChiKid]

The end of the protein sequence after ppp seems to be the same as the carrier in the HIV-TAT1, referencing the article you cited:

Proc Natl Acad Sci U S A. 2007 Dec 26; 104(52): 20805–20810.

Molecular dynamics simulations suggest a mechanism for translocation of the HIV-1 TAT peptide across lipid membranes
Henry D. Herce and Angel E. Garcia*

 

[TaiChiKid]

I would purchase if a small amount such as 10mg or 25mg would be available, allowing more expense for sub-aliquoting.

 

[meatsauce]

The end of the protein sequence after ppp seems to be the same as the carrier in the HIV-TAT1, referencing the article you cited:

Proc Natl Acad Sci U S A. 2007 Dec 26; 104(52): 20805–20810.

Molecular dynamics simulations suggest a mechanism for translocation of the HIV-1 TAT peptide across lipid membranes
Henry D. Herce and Angel E. Garcia*

Nice find and  investigation.

[TaiChiKid]

I never realized the price quoted included approximate shipping.  If 25mg meets the minimum, please include me.

[smithx]

To be clear, I'm not organizing a group buy, just helping out on my own volition by getting some quotes which others could use, from known-reputable suppliers.

 

If you're talking about the estimated shipping on the Genscript quote, that was for shipping all of the vials in one box to one place in the USA. It has nothing to do with the cost of shipping anyone's individual vials to them wherever they might be.

 

 

I never realized the price quoted included approximate shipping.  If 25mg meets the minimum, please include me.

 

[meatsauce]

So far I am going with Genscript. The US company decided not to match the qoute I got from them. I want to start collecting payment. Does anyone have a good recommendation for doing so? I can't use paypal. 

[TaiChiKid]

Guess that lets me out since I take it there will be no forwarding of 10 or 25mg vials, lol

[tintinet]

So far I am going with Genscript. The US company decided not to match the qoute I got from them. I want to start collecting payment. Does anyone have a good recommendation for doing so? I can't use paypal. 

Bitcoin!

 

or Venmo, Cash$, Zelle, etc..

Edited by tintinet, 28 June 2017 - 09:53 PM.

[smithx]

Why wouldn't there be?

 

Guess that lets me out since I take it there will be no forwarding of 10 or 25mg vials, lol

 

[mvlad]

Hi Guys,

 

Joined just to let you guys know we can easily do this. Would like to caution though that this has so far not been trialled on humans and going forward you'd need to be aware of this fact and all it entails. Carefully consider that fact and try not to dismiss it without due consideration, research and diligence.

 

If youd like, we (pioneering private forum-known on here too) can combine our efforts and do this together. Life preservation/extension, anti aging, cognition enhancements and all sorts of improvements are amongst what we pursue at the cutting edge. The lab has already confirmed it 100%, our price is significantly cheaper, we have several years of experience, expertise and track record to prove our ability, authenticity and credibility including with proteins/peptides, and with systems in place to guarantee we get genuine product and to spec.

 

Any questions, feel free to PM or reply.

 

Thanks

[smithx]

mvlad, your post is interesting but lacks any details which would help to understand exactly what you're offering:

 

- What's the name of the group?

- Do you have a website or forum?

- What's the price you are offering?

- Who is manufacturing the peptide?

- How are you verifying identity and purity?

- What is the purity which is being claimed?

- Is TFA being fully removed? Trifluoracetic acid is toxic and has other associated issues: https://www.ncbi.nlm...pubmed/10567002 for example

 

 

[mvlad]

smithx,

 

- What's the name of the group?

PioneeringHairGrowth

- What's the price you are offering?

$680/100mg

- How are you verifying identity and purity?

Whole gauntlet of tests as we usually do inc hplc, ms, lc, and whatever else as need arises up to and inc amino acid analysis and animal testing.

- What is the purity which is being claimed?

98%+

- Is TFA being fully removed?

Yes, obviously

 

Any question left unanswered is because you can google it or its private info. Like I said we have been doing this for over 5 years without a single issue ever and have been tested by others too. You are welcome to retest wherever you'd like again too if you want.

[smithx]

Thanks. You left out the question of who's producing the peptide.

 

By the way, if  I was getting some of this (which I'm not sure I am, yet), I would prefer to pay a bit  more to buy from an established company specializing in this kind of synthesis. But that's just my predilection. Also, GenScript will usually let themselves be negotiated down by 10-20% if you push them, so there's that too.

 

 

Edited by smithx, 01 July 2017 - 02:28 AM.

[mvlad]

Like I stated "Any question left unanswered is because you can google it or its private info". They have all sorts of mad connections and their lab has made it before.

 

 

Their genuineness, authenticity, purity, experience, expertise, connections and OCD focus on quality and looking out for you is beyond reproach. And this in comparison to the other feats they have pulled off is nothing. It is a system that has been working for over 5 years with zero issues in over a hundred projects including numerous proteins/peptides with many many firsts to market.

 

 

The more important question here is whether you guys are dead serious and whether you'd like to join in and combine our efforts.

Edited by mvlad, 01 July 2017 - 02:42 AM.

[smithx]

They have all sorts of mad connections and their lab has made it before.

Their genuineness, authenticity, purity, experience, expertise, connections and OCD focus on quality and looking out for you is beyond reproach.

Except you won't say who they are...

 

Edited by smithx, 01 July 2017 - 03:00 AM.

[NotHenghisHapthorn]

I joined Longecity this week to participate in a FOXO4-DRI group purchase.  I'll buy 500mg (half a gram) up to the price GenScript quoted: $7.70mg US.

 

I'm located in the United States, for shipping purposes.

 

[smithx]

Just for completeness I got a quote from Pepscan, which was the company that made the peptide actually used in the published study. They are somewhat more expensive:

 

FOXO4 DRI, a full d-amino acid peptide H-ltlrkepaseiaqsileaysqnGwanrrsGGkrppprrrqrrkkrG-OH
• 1000mg lyophilized product Price Euro 11,210.00
• C-term; free acid
• N-term; free amine
• pHPLC purification
• Purity 90% up to 99%
• MS-UPLC analysis (UV and Mass)

2 Aliquot production of 5 mg aliquots 400.00

3 Shipping 80.00

All custom peptide synthesis orders are subject to potential synthesis difficulties.Specified purities refer to UPLC purities obtained with linear gradient system (gradient: 5-55% B in 2 min, flow: 1 ml/min, eluent A: 100 %H2O+0.05% TFA; eluent B: 100% CH3CN+ 0.05% TFA; ) using an C18 RP-HPLC column (i.e. C18, 1,7um, 50x2,1mm) and detection at 215nm. Specified columns and gradient systems may be substituted by similar products/gradients with comparable or better resolution without prior notice. Pepscan offers confirmation of purities detected using the routine protocols above by performing secondary analysis using optimized HPLC conditions including different gradient systems, eluents, column materials and dimensions. All orders for custom peptides are accepted by Pepscan Presto B.V. subject to the proviso that, should the peptides prove difficult to synthesize or to purify, we reserve the right to cancel the order or to supply a product at lower yield or purity than quoted. Resynthesis of a peptide will only be undertaken at Pepscan Presto’s direction. Reduced prices will apply where lower mass and/or purity is obtained; the price is scaled in proportion to our list prices. Peptides are delivered based on gross peptide weight, unless stated otherwise. Quantities in μmol or mmol indicate the scale the synthesis of the product is started at (not the amount of deliverable product).

 

 

[smithx]

Based on the fact that all D peptides are unusual, I went back to Genscript to verify that they'd quoted the correct peptide. Apparently they hadn't, which calls into question similar offerings out there on the market. I submitted the exact sequence in the paper, but what they were going to produce was a more typical L isomer peptide.

 

I think that what they are quoting now is the correct peptide, but if people really really want to be certain, getting it from Pepscan and paying the premium could be worth it.

 

The correct code for D-Aa of the this peptide in our system should be:

{d-Leu}{d-Thr}{d-Leu}{d-Arg}{

d-Lys}{d-Glu}{d-Pro}{d-Ala}{d-Ser}{d-Glu}{d-Ile}{d-Ala}{d-Gln}{d-Ser}{d-Ile}{d-Leu}{d-Glu}{d-Ala}{d-Tyr}{d-Ser}{d-Gln}{d-Asn}{d-Gly}{d-Trp}{d-Ala}{d-Asn}{d-Arg}{d-Arg}{d-Ser}{d-Gly}{d-Gly}{d-Lys}{d-Arg}{d-Pro}{d-Pro}{d-Pro}{d-Arg}{d-Arg}{d-Arg}{d-Gln}{d-Arg}{d-Arg}{d-Lys}{d-Lys}{d-Arg}{d-Gly}

 

The price is a little higher than L-Aa (the sequence you submitted). Please help to confirm.

Attached please find the updated quote with correct sequence/price.

Unit Price: $10042.64 Discount: $3012.79 Extended Price: $7029.85

SC1690: Guaranteed TFA removal:FOXO4 D-Retro-
Inverso peptide; Guaranteed Hydrochloride : $810

Total including Shipping: $7,877.03

NOTE: This quote includes a 30% discount promotion which ends July 31, 2017.

 

 

 

Edited by smithx, 10 July 2017 - 06:06 PM.

[Vajra]

Hi Smithx,

 

Count me in on getting it from Pepscan. 

 

Thanks

 

Eli

[smithx]

Just to clarify, I'm not doing the group buy. I'm just getting information for people.

 

I'm not even certain I would try it myself at this point, because it hasn't been tested people yet.