DAC (Drug Affinity Complex) to increase the half life of many peptides

[drtbear1967]

<!-- /react-text --><time title="Mar 10, 2017" class="_379kp" datetime="2017-03-11T00:10:21.000Z"></time> theguerillachemist<!-- react-text: 39 -->

I get this question a lot bc I think there is some bad info on message boards. Drug Affinity Complex(DAC) is a delivery technology developed by ConjuChem in order to protect peptides from rapid degrading and metabolism by the kidneys. A peptide is "chopped" up by enzymes called peptidases, usually very rapidly. By attaching the synthetic DAC portion to the peptide, it is able to extend the half life from several minutes up to 7 days. If you look at the structure here, you'll see the DAC includes a "linker" molecule and a maleimide molecule which binds to albumin, a protein found in your blood. Covalent attachment to albumin can block both cleavage by peptidases and various mechanisms of clearance of a variety of peptides. Once in the body, the DAC moiety increases bioavailability, as well. So to sum up: DAC can increase the half life of many peptides like GRF1-29(CJC-1295 is GRF1-29 plus DAC)by decreasing the activity of peptidases. It also increases bioavailability and maintains biological activity. This study definitively shows there is no "bleed" from CJC-1295. I recommend going with this option over certain peptides without DAC so you can enjoy the benefits of the peptide without injecting multiple times a day

 

[BigZ]

I've heard a lot about this particular component. What exactly is the "bleed" supposed to be? That's the only thing I couldn't definitively figure out and why it was supposedly bad. There was just a lot of hearsay where many were saying there was a "bleed."

 

[drtbear1967]

The bleed myth comes from all the bro science out there on the internet. They're people that say that you need a pulse of gh several times during the day to see positive effects. However others feel that a constant release (bleed) of GH throughout the day is better off than the pulse. There is a lot of science that can be found both pro and con.

 

[iloveolego]

hi!
i've just found very confusing information about DAC on the ConjuChem website

In addition, conjugation of the drug to albumin allows for a wide distribution of DAC™ compounds throughout the body—with the exception of the brain because the DAC™ usually does not cross the blood-brain barrier

http://www.conjuchem.com/technology/dac

this means almost all BB peptides like GRF GHRP etc. would become ineffective with DAC, including CJC 1295. Because they show their activities in HG release only in brain
and all studies of CJC 1295 is fake?
what do you guys think about it?

 

[Presser]

hi!
i've just found very confusing information about DAC on the ConjuChem website

http://www.conjuchem.com/technology/dac

this means almost all BB peptides like GRF GHRP etc. would become ineffective with DAC, including CJC 1295. Because they show their activities in HG release only in brain
and all studies of CJC 1295 is fake?
what do you guys think about it?

So your asking whether or not these peptides with the DAC attachment are rendered useless due to the DAC’s inability to cross the blood / brain barrier due to the pituitary gland being part of the brain and unable to produce the extra pulses of growth hormone?

Is that what your asking brutha

 

[Presser]

And I have to say thats a quite logical questions on its face, though im unsure of the answer lmao, I do know the pituitary gland is at the base of the brain and part of the endocrine system, so in short I do not believe your hypothesis is correct, but I could be very very wrong. Either way that was quite a good question for which im not entirely positive

 

[Presser]

And for anyone else who wants to read more on DAC , below is a more specific explanation:

About DAC™


The Drug Affinity Complex (DAC™) technology developed by ConjuChem addresses the longstanding challenge of protecting peptides from peptidase degradation as well as preventing rapid kidney excretion in order to make development of peptide drugs practicable. Our DAC™ technology is based on two features:

• A synthetic modification of a well characterized peptide moiety can yield a modified peptide analogue containing a reactive chemical group but still retaining most of its original biologic activity; the modified peptide is called a drug affinity complex (DAC™)
• The attachment of the DAC™ through reaction of the active moiety with the free thiol of cysteine-34 of albumin

The conjugation of a DAC™ to albumin can occur in two ways: in vivo to circulating albumin following parenteral administration, or ex vivo to recombinant or purified albumin, which is then administered parenterally as a preformed conjugate. The covalent attachment of a DAC™ to albumin is permanent so the peptide does not need to be released from its albumin carrier in order to perform its biologic function. The plasma half-life of albumin varies within species: 40 to 48 hours in rats, approximately 60 hours in dogs, and around 15 days in humans.

There are three parts of each DAC™ construct:

• The drug component (the portion responsible for biologic activity)
• A linker attached to the drug component
• A reactive chemistry group at the opposite end of the linker, usually a soft electrophile selective for thiols; a maleimide is the most useful embodiment

Natural peptides usually degrade rapidly and are quickly cleared from circulation. Covalent attachment to albumin can block both cleavage by peptidases and various mechanisms of clearance of a wide variety of peptides independent of structure, activity, and therapeutic category. In addition, conjugation of the drug to albumin allows for a wide distribution of DAC™ compounds throughout the body—with the exception of the brain because the DAC™ usually does not cross the blood-brain barrier.

The reaction of the DAC™ in vivo is highly selective for serum albumin over other protein alternatives. This is due to the presence of far higher concentrations of albumin in plasma and interstitial fluids, and because it contains a more reactive thiol group (pK ~5.0) than other molecules, such as cysteine (pK ~8.5) and gluthathione (pK ~8.9) found in plasma and lymph. Also, in physiologic state, the thiol of albumin’s cysteine-34 is in its most reactive state (S-anion) towards electrophiles such as maleimide.

 

[Macho313]

The bleed myth comes from all the bro science out there on the internet. They're people that say that you need a pulse of gh several times during the day to see positive effects. However others feel that a constant release (bleed) of GH throughout the day is better off than the pulse. There is a lot of science that can be found both pro and con.

2 questions for your brother the first one is do you think CJC with or without deck would be beneficial to igf-1 lr3? The second question is and tried a IGF every way possible throughout the years, post workout, pre-workout, in the morning on workout days,and non workout days. Do you believe not the right way to dose igf-1 lr3 is on your days off from training? for instance because of my body,and how lean I Stay I only work out 4 days a week. I came across a a article by Mike Arnold about a year ago. I think it was by him but anyway they were saying that being that igf-1lr3 has a 23 to 24 hour half life, you should take it on non training days because if you take it on training days whether it's in the morning, pre-workout, or post workout, that igf blunts the release of MGF which we need to grow? Just wanted to get your feedback on that brother and was wondering what you feel like the best way to run it? Also do you stack it with insulin or GH or just run it by itself?

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