This is a working overview of DAC linker, written for readers who want more than a one-paragraph summary but less than a textbook.
This page was last updated on 2026-08-01 and is reviewed periodically as new material appears.
Two related forms circulate in technical discussion under the same family name. The original version carries a drug affinity complex (DAC) that binds covalently to serum albumin after administration, and this linkage substantially extends circulation time. A second form, frequently written as modified GRF(1-29) or CJC-1295 without DAC, lacks that linker and clears much faster. The naming is a frequent source of confusion because the shorthand CJC-1295 can refer to either form depending on the source. Reports sometimes fail to specify which variant was studied.
The peptide backbone includes a D-alanine at position two, which resists cleavage by dipeptidyl peptidase IV, and several other substitutions that reduce degradation. Its molecular weight is roughly 3.4 kDa without the linker and about 3.6 kDa with it. The molecule is water soluble and is normally supplied as a lyophilized powder. Precise sequence and mass values depend on which variant is described, so technical documents usually state the exact form being referenced.
CJC-1295 is a synthetic analogue of growth hormone-releasing hormone, built on the 29-amino-acid GHRH(1-29) fragment. Four substitutions distinguish it from the natural sequence: D-alanine at position 2, glutamine at position 8, alanine at position 15, and leucine at position 27. These changes reduce enzymatic cleavage and extend the peptide's persistence in circulation. The compound is discussed in two forms, one carrying a drug affinity complex and one without it.
The drug affinity complex is a maleimidopropionic acid group attached to a lysine side chain. It reacts with the free thiol of cysteine-34 on circulating albumin, forming a covalent bond. This conjugation keeps the peptide in the bloodstream and shields it from rapid renal filtration and proteolysis. Reported circulation half-lives for the albumin-bound form fall in the range of roughly six to nine days in early human studies.
| Property | Value | Notes |
|---|---|---|
| Molecular weight (no linker) | ~3.37 kDa | Calculated from peptide sequence |
| Molecular weight (with linker) | ~3.65 kDa | Includes albumin-binding moiety |
| Appearance | White to off-white powder | Typically lyophilized |
| Solubility | Soluble in water | Also dissolves in aqueous buffers |
| Common synonyms | Modified GRF(1-29), DAC:GRF | Usage varies by source |
CJC-1295 acts at the growth hormone-releasing hormone receptor, a G-protein-coupled receptor found on somatotroph cells in the anterior pituitary. Binding triggers a rise in cyclic AMP and calcium entry, which promotes release of stored growth hormone. Because the peptide mimics the body's own releasing hormone, it amplifies existing secretory pulses rather than driving continuous output. The size of the response therefore depends partly on the subject's own hormonal rhythm and feedback state.
The attached maleimide group explains the unusual duration of the DAC version. After injection it reacts with the thiol of cysteine-34 on serum albumin, forming a stable covalent bond. The resulting conjugate is too large for rapid kidney filtration and is shielded from many peptidases. Reported half-lives for this form reach several days, whereas the version without the group is cleared in roughly half an hour. That gap is the main pharmacological difference between the two.
Downstream of growth hormone, the liver and other tissues increase production of insulin-like growth factor 1, a mediator of many growth-promoting effects. Studies have documented elevated levels of both hormones after dosing, and the rise from the long-acting form persists longer than that produced by shorter-acting analogues. What remains unclear is whether sustained elevation of these markers translates into meaningful clinical benefit, and whether prolonged exposure carries risks that short trials could not detect.
CJC-1295 belongs to a class of synthetic peptides modeled on growth hormone releasing hormone, a forty-four amino acid signal produced by the hypothalamus. The compound is built from the first twenty-nine residues of the natural sequence, with four substitutions introduced at positions 2, 8, 15 and 27. These changes were designed to slow enzymatic breakdown while preserving receptor activation. The result is a peptide that is shorter than native GHRH and considerably more resistant to ordinary clearance pathways in circulation.
Two related forms appear under the CJC-1295 name. The simpler analogue, commonly written as modified GRF(1-29), carries the four substitutions but no additional conjugation. The second form attaches a maleimidopropionic acid linker to a lysine residue, a modification frequently called the drug affinity complex. That linker reacts with the free thiol on serum albumin to form a covalent bond. Because albumin has a long residence time in blood, the conjugated peptide stays in circulation far longer than the unconjugated analogue.
Binding of the peptide to the growth hormone-releasing hormone receptor on pituitary somatotrophs triggers a G protein coupled cascade that raises cyclic AMP and opens calcium channels. The result is greater secretion of growth hormone into the bloodstream. Because the peptide acts at the same receptor as the natural hypothalamic hormone, its effect is amplified pulse size rather than an entirely separate release pathway. Receptor binding alone does not determine the response, since somatostatin tone and other inputs modulate the final output.
The albumin-binding version stays in circulation for days, because covalent attachment to serum albumin shields the peptide from rapid filtration and degradation. Reported half-lives for this form fall in the range of several days. The version without the linker is cleared in minutes, with estimates often near thirty minutes in animal work. These figures come from small studies and vary with assay method, species, and route, so they are best read as approximate rather than fixed constants.
Another influence is over-hunting and poaching, which can reduce the overall population of game animals, especially those located near villages, as in the case of peccaries. The effects of poaching can especially be seen in the ivory trade with African elephants. Marine mammals are at risk from entanglement from fishing gear, notably cetaceans, with discard mortalities ranging from 65,000 to 86,000 individuals annually. Attention is being given to endangered species globally, notably through the Convention on Biological Diversity, otherwise known as the Rio Accord, which includes 189 signatory countries that are focused on identifying endangered species and habitats. Another notable conservation organization is the IUCN, which has a membership of over 1,200 governmental and non-governmental organizations. Recent extinctions can be directly attributed to human influences. The IUCN characterizes 'recent' extinction as those that have occurred past the cut-off point of 1500, and around 80 mammal species have gone extinct since that time and 2015. Some species, such as the Père David's deer are extinct in the wild, and survive solely in captive populations. Other populations, such as the Florida panther, are ecologically extinct, surviving in such low numbers that they essentially have no impact on the ecosystem. Other populations are only locally extinct (extirpated), still existing elsewhere, but reduced in distribution, as with the extinction of gray whales in the Atlantic.
=== Drowsiness === Clonazepam, like other benzodiazepines, may impair a person's ability to drive or operate machinery. The central nervous system depressing effects of the drug can be intensified by alcohol consumption, so alcohol should be avoided while taking this medication. Benzodiazepines have been shown to cause dependence. Patients dependent on clonazepam should be slowly titrated off under the supervision of a qualified healthcare professional to reduce the intensity of withdrawal or rebound symptoms.
Merck & Co. adapted the 1936 laboratory-scale synthesis, allowing them to manufacture thiamine in Rahway in 1937. However, an alternative route using the intermediate Grewe diamine (5-(aminomethyl)-2-methyl-4-pyrimidinamine), first published in 1937, was investigated by Hoffman La Roche and competitive manufacturing processes followed. Efficient routes to the diamine have continued to be of interest. In the European Economic Area, thiamine is registered under REACH regulation and between 100 and 1,000 tonnes per annum are manufactured or imported there.
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Other notable derivatives then result from further modification of this template, with saturation of the 7,8-double bond of etorphine resulting in the even more potent dihydroetorphine (up to 12,000× potency of morphine) and acetylation of the 3-hydroxy group of etorphine resulting in acetorphine (8700× morphine). While the isopentyl homologue of etorphine, known as M-140, is nearly three times more potent, its 7,8-dihydro and 3-acetyl derivatives are less potent than the corresponding derivatives of etorphine at 11,000 and 1300 times morphine, respectively. Replacing the N-methyl group with cyclopropylmethyl results in opioid antagonists such as diprenorphine (M5050, which is used as an antidote to reverse the effects of etorphine, M99), and partial agonists such as buprenorphine, which is widely used in the treatment of opioid addiction, although conversely the N-cyclopropylmethyl derivative of M-140, which has the code number M-320, retains similarly potent μ-opioid full agonist activity to the N-methyl derivative. More complex substitutions on the ring system can be used to produce selective δ-opioid agonists such as BU-48, and selective κ-opioid agonists such as CL 110,393.
== Research == The research name of emapalumab was NI-0501. A phase II/III trial began in 2013 and is ongoing as of August 2018. The trial targets patients under the age of 18 who have failed to improve on conventional treatments. This study was realised in the context of an EU-funded FP7 project, named FIGHT-HLH (306124).
will begin restricting travel from India starting May 4 due to rising cases of the Lineage B.1.617 which originated in the latter country. Michigan reports its first case of Lineage B.1.617, first discovered in India, in a person from Clinton County.
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On August 23, 2012, further results were published in the U.S. journal PLOS ONE in collaboration with Motoharu Seiki of the University of Tokyo Institute of Medical Science. By 2014, the technology had advanced to the stage of detecting Alzheimer’s-related substances directly from blood samples, and since April 2014, efforts under a new framework have been directed toward practical application.
Heart rate reduction, i.e., decrease of the resting heart rate (negative chronotropic effect) and reduction of excessive elevations resulting from exercise or stress. Reduction of the force of contraction, i.e., decrease in contractility (negative inotropic effect), which lessens how hard each heartbeat contracts. Decrease in cardiac output, i.e., decrease in both heart rate and contractility within myocardium cells, where β1 is predominantly located, overall blood output per minute lowers called cardiac output/dysfunction, allowing decreased demands placed onto impaired hearts, reducing oxygen demand-supply mismatch. Lowering of blood pressure. Antiarrhythmic effects, such as supraventricular tachycardia prevention. Metoprolol also prevents electrical wave propagation. Metoprolol inhibits CYP2J2.
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Sources: en.wikipedia.org
No. It is a synthetic analogue modeled on the first 29 residues of human GHRH. The substitutions and any linker are laboratory modifications rather than features of the endogenous peptide.
Early development used the albumin-binding form, and a shorter variant was later discussed under the same label. Because the two differ in half-life and handling, ambiguity arises whenever a source omits the variant designation.
The compound derives from that fragment but is not identical to it. The parent fragment lacks the stabilizing substitutions, so its degradation rate and duration of action differ noticeably.
The two share the same 29-amino-acid backbone. CJC-1295 carries an additional albumin-binding moiety that markedly extends its residence time in circulation, while the form without that moiety clears faster. Literature sometimes applies the name loosely to either variant.