DAC linker comes up often in conversation and rarely with the context attached. Here we lay out the basics in order, then work through the practical considerations.
Last reviewed on 2025-10-22. Where a claim depends on a specific study, the study is described rather than over-claimed.
The compound emerged from work at a Canadian biotechnology firm in the early 2000s. Early human studies examined its effect on growth hormone and insulin-like growth factor 1 in healthy volunteers and in people with HIV-associated fat redistribution. Reports described sustained increases in both markers after a single injection. Development did not advance to regulatory approval, and the clinical programme was later discontinued. The molecule is now encountered mainly as a research chemical rather than a marketed medicine.
Two forms circulate in research settings and are frequently confused. One carries the drug affinity complex and is often written as CJC-1295 with DAC; the other lacks that group and is usually called modified GRF(1-29). The two share the same core sequence but differ sharply in how long they persist in blood. Products labelled only as CJC-1295 normally refer to the version carrying the complex. Documentation that omits the distinction leaves the intended molecule ambiguous.
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.
Receptor level activity follows the canonical GHRH pathway. The peptide binds the GHRH receptor, a class B G protein coupled receptor on somatotroph cells of the anterior pituitary. Binding raises intracellular cyclic AMP, which promotes calcium entry and the release of growth hormone into the bloodstream. Because the molecule acts at the same receptor as the endogenous hormone, its effect is superimposed on the natural pulsatile rhythm rather than replacing it. Whether sustained receptor occupation leads to desensitization is not fully settled.
| Property | Value | Notes |
|---|---|---|
| Molecular formula | C152H252N44O42 | Cited for the form without the drug affinity complex |
| Molecular weight | About 3368 Da | Reported value for modified GRF(1-29) |
| Appearance | White to off-white powder | Lyophilised solid as usually supplied |
| Solubility | Soluble in water and polar solvents | Clarity depends on purity and salt content |
| Typical storage | -20 C or below, dry | Protect from light and repeated warming cycles |
The peptide backbone corresponds to GRF(1-29), the first 29 residues of native growth hormone-releasing hormone, which retains most of the receptor-activating activity of the full-length molecule. Four substitutions distinguish the analog from the natural sequence: D-alanine at position 2, glutamine at position 8, alanine at position 15, and leucine at position 27. These changes slow cleavage by dipeptidyl peptidase IV, the enzyme that degrades native hormone in plasma within minutes. The outcome is improved enzymatic stability combined with a still brief residence time when no additional modification is present.
Naming in this area is inconsistent, and readers should treat product labels with care. In much of the literature and in vendor catalogs, the unqualified term refers to the albumin-binding version, while the version lacking the DAC group appears as modified GRF(1-29), mod GRF(1-29), or the same name with a without-DAC qualifier. Because one abbreviation has been applied to both materials, the only reliable way to identify a sample is to check the stated sequence and the presence of the linker.
CJC-1295 is the name used for a synthetic peptide modeled on growth hormone-releasing hormone, the hypothalamic signal that prompts the pituitary to release growth hormone. The compound was described by a Canadian drug discovery company in the mid-2000s as a long-acting research tool. Two closely related molecules share the name in practice: one carries a drug affinity complex, or DAC, group, and one does not. The distinction matters because the two behave differently in circulation.
Once in circulation, the peptide binds the growth hormone-releasing hormone receptor displayed on pituitary somatotroph cells. Receptor activation couples to Gs proteins, elevates intracellular cyclic AMP, and drives protein kinase A signaling inside the cell. That cascade increases discharge of growth hormone into the bloodstream. The analog therefore operates through a receptor pathway that already exists for the body's own releasing hormone, rather than through an engineered artificial target.
Clearance profiles diverge sharply between the two versions. The albumin-binding molecule stays in plasma for several days, whereas the unmodified analog is largely gone within about half an hour in reported work. Cleavage by dipeptidyl peptidase IV is a major contributor to the short life of the unmodified sequence. These gaps mean the two versions cannot be substituted for each other in study design or in reading results side by side.
Reports on this compound commonly follow serum growth hormone and insulin-like growth factor 1 across defined time windows. Protocols differ in sampling frequency, assay platform, and participant characteristics, which makes direct comparison between publications difficult. Some work focuses on pulsatile release patterns instead of average concentrations. Whether repeated exposure alters endogenous hormone rhythms over long periods remains an open question, and the formal literature is thinner than the volume of informal commentary implies.
A catch bond is a type of noncovalent bond whose dissociation lifetime increases with tensile force applied to the bond. Normally, bond lifetimes are expected to diminish with force. In the case of catch bonds, the lifetime of the bond actually increases up to a maximum before it decreases like in a normal bond. Catch bonds work in a way that is conceptually similar to that of a Chinese finger trap. While catch bonds are strengthened by an increase in force, the force increase is not necessary for the bond to work. Catch bonds were suspected for many years to play a role in the rolling of leukocytes, being strong enough to roll in presence of high forces caused by high shear stresses, while avoiding getting stuck in capillaries where the fluid flow, and therefore shear stress, is low. The existence of catch bonds was debated for many years until strong evidence of their existence was found in bacteria. Definite proof of their existence came shortly thereafter in leukocytes.
The manufacturer recommends a "double pour" serve, which according to Diageo should take two minutes. Guinness has promoted this wait with advertising campaigns such as "good things come to those who wait". The brewer recommends that draught Guinness should be served at 6–7 °C (42.8 °F), while Extra Cold Guinness should be served at 3.5 °C (38.6 °F). Before the 21st century, it was popular to serve Guinness at cellar temperature (about 13 °C) and most drinkers preferred it at room temperature (about 20 °C). According to Esquire magazine, a pint of Guinness should be served in a slightly tulip-shaped pint glass, rather than the taller European tulip or 'Nonic' glass, which contains a ridge approx 3/4 of the way up the glass. To begin the pour, the server holds the glass at a 45° angle below the tap and fills the glass 3/4 full. On the way out of the tap, the beer is forced at high speed through a five-hole disc restrictor plate at the end of the tap, creating friction and forcing the creation of small nitrogen bubbles which form a creamy head. The server brings the glass from 45° angle to a vertical position. After allowing the initial pour to settle, the server pushes the tap handle back and fills the remainder of the glass until the head forms a slight dome over the top of the glass (or "just proud of the rim"). Guinness recommends that, to avoid the bitter taste of the nitrogen foam head, gulps should be taken from the glass rather than sipping the drink. In 2010, Guinness redesigned their pint glass for the first time in a decade.
=== Mechanism of toxicity in humans === After FIAU is converted to FIAU-TP, it is not only available to viral polymerase, in humans it can also be taken up into mitochondria and used by mitochondrial DNA polymerase γ (POLG). When FIAU is incorporated into mitochondrial DNA (mtDNA), it disrupts mtDNA replication, which leads to mtDNA depletion. With less mtDNA, cells can make fewer proteins for the electron transport chain, so oxidative phosphorylation fails. The consequences are lactic acidosis (shift to anaerobic metabolism) and microvascular steatosis (impaired fatty-acid oxidation), especially in the liver
Sources: en.wikipedia.org
== Further reading == Food and Nutrition Information Center. "Dietary Supplements: General Resources for Consumers" (PDF). National Agricultural Library. Archived from the original (PDF) on 2008-12-16. List of resources that provides an overview of herbal and dietary supplements, including use, regulation, research, and cautionary information. "Questions to Ask Before Taking Vitamin and Mineral Supplements". nutrition.gov. Archived from the original on 2017-06-22. "Dietary Supplement Fact Sheets". NIH Office of Dietary Supplements.
In 2011 there were approximately 12,000 students in all disciplines in Le Havre. Opened in 1986, the University of Le Havre is recent, medium-sized and well located: the largest campus is virtually in the centre of the city near railway and tram stations. The campus includes a University Library (2006), a gym, several dining halls with student housing, a structure incorporating a theatre, an orientation service, and student associations. In 2010–2011, 6,914 students were enrolled including 5,071 undergraduates, 1,651 Masters students, and 192 postgraduate students. The university also trains 317 engineering students including the Logistical Studies Higher Education Institute (ISEL). It offers 120 Diplomas of State prepared by the Faculty of Science and Technology, Faculty of International Affairs, and the Faculty of Arts and Humanities. Many courses are offered are related to the port operations, logistics, industry, and sustainable development. Twelve languages are taught and 17% of students are foreigners. The University of Le Havre is also a research centre with nine laboratories. It works in partnership with other higher education institutions (INSA Rouen, IEP, IUFM, and Normandy University). The University Institutes of Technology of Le Havre occupies two main sites: one in the upper town in the Caucriauville-Rouelles district which was opened in 1967 and another in the Eure district since 2011. The IUT has a total of 1,881 students divided into ten departments preparing for the DUT.
== Early career == Shambhu Nath De was born in Hooghly District, West Bengal, India. His father Mr Dasarathi De was a not so successful businessman. Supported by his uncle Asutosh De, De completed the Matriculation examination with distinction from Garbati High School that helped him to get the District scholarship as well as to pursue further education in Hooghly Mohsin College, which was then affiliated with the prestigious University of Calcutta. His higher education was supported by Kestodhan Seth, who identified De as an extraordinary student. De passed his M.B. examination in 1939 from Calcutta Medical College and completed a Diploma in Tropical Medicine (DTM) in 1942. Soon after graduation he joined Calcutta Medical College as a Demonstrator of Pathology and initiated his research under Professor B. P. Tribedi. In 1947, De joined as a PhD student under Sir Roy Cameron at the Department of Morbid Anatomy, University College Hospital Medical School, London, and obtained his PhD degree in Pathology in 1949. After his return, De worked on pathogenesis of cholera and started publishing his findings. In 1955, De became the Head of Pathology and Bacteriology Division of the Calcutta Medical College, which he continued until his retirement. De published more than 30 research papers and has written an excellent monograph on cholera and its pathogenesis.
== Parental care == Blow flies like C. vomitoria lay their eggs at carrion sites, which are scarce in most places so these corpses end up with many eggs of various species. As a result, high larval density arises. In fact, when there are many other individuals around the site, pregnant females increase oviposition rate (which increases number of offspring), likely triggered by contact and chemical stimulation. However, the large number of larvae ends up being beneficial for each individual. The larvae feed by secretion of enzymes that break down tissues of the corpse, so by aggregating in large numbers these secretions are more effective, leading to easier feeding. Additionally, the large aggregation helps generate heat and keep the larvae warm, as the flies generally prefer warmer temperature. One complication with the high number of individuals is that competition is still a factor, as larvae on the periphery may be left out of the feeding, and by the end of the developmental cycle they emerge undernourished and undersized.
Sources: en.wikipedia.org
=== Vitamin B12-dependent enzymes === The cobalt-containing Vitamin B12 (also known as cobalamin) catalyzes the transfer of methyl (−CH3) groups between two molecules, which involves the breaking of C−C bonds, a process that is energetically expensive in organic reactions. The metal ion lowers the activation energy for the process by forming a transient Co−CH3 bond. The structure of the coenzyme was famously determined by Dorothy Hodgkin and co-workers, for which she received a Nobel Prize in Chemistry. It consists of a cobalt(II) ion coordinated to four nitrogen atoms of a corrin ring and a fifth nitrogen atom from an imidazole group. In the resting state there is a Co−C sigma bond with the 5′ carbon atom of adenosine. This is a naturally occurring organometallic compound, which explains its function in trans-methylation reactions, such as the reaction carried out by methionine synthase.
The gastrin-releasing peptide receptor (GRPR), now properly known as BB2 is a G protein-coupled receptor whose endogenous ligand is gastrin releasing peptide. In humans it is highly expressed in the pancreas and is also expressed in the stomach, adrenal cortex and brain. Gastrin-releasing peptide (GRP) regulates numerous functions of the gastrointestinal and central nervous systems, including release of gastrointestinal hormones, smooth muscle cell contraction, and epithelial cell proliferation and is a potent mitogen for neoplastic tissues. The effects of GRP are mediated through the gastrin-releasing peptide receptor. This receptor is a glycosylated, 7-transmembrane G-protein coupled receptor that activates the phospholipase C signaling pathway. The receptor is aberrantly expressed in numerous cancers such as those of the lung, colon, and prostate. An individual with autism and multiple exostoses was found to have a balanced translocation between chromosome 8 and an X chromosome breakpoint located within the gastrin-releasing peptide receptor gene. The transcription factor CREB is a regulator of human GRP-R expression in colon cancer. Activation MOR1D‐GRPR heteromers in the spinal cord mediate the common troublesome opioid-induced itch.
Arapaima can reach lengths of more than 2 m (6 ft 7 in), in some exceptional cases even exceeding 2.6 m (8 ft 6 in) and over 100 kg (220 lb). The maximum recorded weight for the species is 200 kg (440 lb), while the longest recorded length verified was 3.07 m (10 ft 1 in). Anecdotal reports suggest that specimens as long as 4.57 m (15 ft 0 in) exist, but verification is deemed impossible, and thus considered questionable. As a result of overfishing, arapaima more than 2 m (6 ft 7 in) are seldom found in the wild. The arapaima is torpedo-shaped, with large, blackish-green scales and red markings. It is streamlined and sleek, with its dorsal and anal fins set near its tail. Arapaima scales have a mineralised, hard, outer layer with a corrugated surface under which lie several layers of collagen fibres in a Bouligand-type arrangement. In a structure similar to plywood, the fibres in each successive layer are oriented at large angles to those in the previous layer, increasing toughness. The hard, corrugated surface of the outer layer, and the tough internal collagen layers work synergistically to contribute to their ability to flex and deform while providing strength and protection—a solution that allows the fish to remain mobile while heavily armored. The arapaima has a fundamental dependence on surface air to breathe. In addition to gills, it has a modified and enlarged swim bladder, composed of lung-like tissue, which enables it to extract oxygen from the air.
Sources: en.wikipedia.org
It is a synthetic peptide analogue of growth hormone-releasing hormone. Four substitutions in its sequence make it more resistant to enzymatic degradation than the natural hormone. In the version carrying a drug affinity complex, the peptide binds albumin and remains in circulation for days.
No regulatory agency has approved CJC-1295 for clinical use. Human trials were conducted in the 2000s, but the development programme was discontinued before any marketing application succeeded. Material sold today is offered as a research chemical, and its purity depends on the supplier.
Sermorelin is an unmodified fragment of growth hormone-releasing hormone and is cleared quickly. CJC-1295 contains substitutions that resist breakdown, and the form with a drug affinity complex persists much longer. Both act at the same receptor but differ substantially in duration of action.
The names are often used interchangeably in casual writing, but they are not strictly identical. Modified GRF(1-29) refers to the unconjugated analogue carrying only the four substitutions. The version sold as CJC-1295 with DAC includes the albumin binding linker and clears much more slowly.