A practical reference on GRF(1-29): what it is, how it behaves, what the literature reports, and where the honest uncertainties sit.
Reviewed 2026-03-06. Anything still debated is marked as such rather than presented as settled.
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 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.
Lyophilized material is generally stable for extended periods when held at minus twenty degrees Celsius or below and protected from moisture and light. In solution the peptide is more labile; bond hydrolysis, aggregation and oxidation of susceptible residues all proceed faster at ambient temperature. Repeated freeze and thaw cycles should be avoided because they promote clumping and loss of soluble material. The conjugated variant adds a further consideration, since the maleimide group can hydrolyze in aqueous buffer and lose its ability to react with albumin.
Laboratory handling centers on minimizing exposure to water, heat and oxygen before use. Working solutions are typically prepared in sterile water or a mild buffer, and any residual particulate matter is removed by filtration. When the powder dissolves slowly, a small proportion of acetonitrile or dilute acetic acid is sometimes added as a co-solvent. Containers are kept sealed and desiccated between uses. Records of lot number, reconstitution date and storage conditions support later comparison of results across experiments.
Identity and purity are established with reversed phase high performance liquid chromatography coupled to mass spectrometry. The chromatographic step separates the target peptide from truncated sequences and deletion products, while the mass measurement confirms the expected molecular weight to within a fraction of a dalton. Because the two common variants differ by the presence of the linker, mass alone can distinguish them in the unconjugated state. Amino acid analysis and peptide mapping are used when sequence level confirmation is required.
| Property | Value | Notes |
|---|---|---|
| Primary target | GHRH receptor | G-protein-coupled receptor on pituitary somatotrophs |
| Half-life, long-acting form | Several days | Extended by covalent albumin binding |
| Half-life, short form | About 30 minutes | Cleared rapidly by peptidases and kidneys |
| Route in studies | Subcutaneous injection | Used in the published human trials |
| Main measured effect | Rise in GH and IGF-1 | Surrogate markers rather than clinical endpoints |
Both forms act at the pituitary receptor for growth hormone-releasing hormone and increase growth hormone output, which in turn raises insulin-like growth factor 1. A long-acting analog produces sustained rather than pulsatile stimulation, and the physiological consequences of that pattern are not fully settled. Published human data on the extended form remain limited, and much of what circulates in discussion traces to early company reports rather than independent replication. How sustained exposure affects normal feedback remains an open question.
The distinguishing feature of the DAC form is a maleimide-containing group that reacts with the free thiol of cysteine-34 on human serum albumin. This reaction forms a covalent bond without enzymatic assistance, and it takes place after the peptide enters the bloodstream. Because albumin is abundant and long-lived, the attached peptide is carried through circulation far longer than an unmodified fragment would survive. The chemistry is a deliberate pharmacokinetic strategy rather than a change to receptor activity.
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.
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.
=== Industry and legal actions === DuPont has used PFOA for over 50 years at its Washington Works plant. Area residents sued DuPont in August 2001 and claimed DuPont released PFOA in excess of their community guideline of 1 part per billion resulting in lower property values and increased risk of illness. The class was certified by Wood Circuit Court Judge George W. Hill. As part of the settlement, DuPont has paid for blood tests and health surveys of residents believed to be affected. Participants numbered 69,030 in the study, which was reviewed by three epidemiologists—the C8 Science Panel—to determine if any health effects are the likely result of exposure. On December 13, 2005, DuPont announced a settlement with the EPA in which DuPont would pay US$10.25 million in fines and an additional US$6.25 million for two supplemental environmental projects without any admission of liability. On September 30, 2008, Chief Judge Joseph R. Goodwin of the United States District Court for the Southern District of West Virginia denied the certification of a class of Parkersburg residents exposed to PFOA from DuPont's facility because they did not "show the common individual injuries needed to certify a class action". On September 28, 2009, Judge Goodwin dismissed the claims of those residents except for medical monitoring. By 2015, more than three thousand plaintiffs have filed personal-injury lawsuits against DuPont. In 2017, DuPont reached a $670.7 million cash settlement related to 3,550 personal injury lawsuits tied to PFOA contamination of drinking water in the Parkersburg area.
== Beneficial and conditional mutations == Although mutations that cause changes in protein sequences can be harmful to an organism, on occasions the effect may be positive in a given environment. In this case, the mutation may enable the mutant organism to withstand particular environmental stresses better than wild-type organisms, or reproduce more quickly. In these cases a mutation will tend to become more common in a population through natural selection. That said, the same mutation can be beneficial in one condition and disadvantageous in another condition. Examples include the following: HIV resistance: a specific 32 base pair deletion in human CCR5 (CCR5-Δ32) confers HIV resistance to homozygotes and delays AIDS onset in heterozygotes. One possible explanation of the etiology of the relatively high frequency of CCR5-Δ32 in the European population is that it conferred resistance to the bubonic plague in mid-14th century Europe. People with this mutation were more likely to survive infection; thus its frequency in the population increased. This theory could explain why this mutation is not found in Southern Africa, which remained untouched by bubonic plague. A newer theory suggests that the selective pressure on the CCR5 Delta 32 mutation was caused by smallpox instead of the bubonic plague. Malaria resistance: An example of a harmful mutation is sickle-cell disease, a blood disorder in which the body produces an abnormal type of the oxygen-carrying substance haemoglobin in the red blood cells.
If Gaddafi's Free Officers had not preempted the Shelhis, they would have almost certainly been defeated by the combined forces of Abdul Aziz Shelhi, the deputy commander of Libya's army, and the prominent families in Cyrenaica that supported the Shelhi family. On 1 September, Gaddafi's Free Officers occupied airports, police depots, radio stations, and government offices in Tripoli and Benghazi. Gaddafi took control of the Berka barracks in Benghazi, while Umar Muhayshi occupied Tripoli barracks and Jalloud seized the city's anti-aircraft batteries. Khweldi Hameidi took over the Tripoli radio station and arrested crown prince Sayyid Hasan ar-Rida al-Mahdi as-Sanussi, forcing him to relinquish his claim to the throne. They met no serious resistance and wielded little violence against the monarchists. Once Gaddafi removed the government, he announced the foundation of the Libyan Arab Republic. Addressing the populace by radio, he proclaimed an end to the "reactionary and corrupt" regime, "the stench of which has sickened and horrified us all". Due to the coup's bloodless nature, it was initially labelled the "White Revolution", although was later renamed the "One September Revolution" after its date. Gaddafi insisted that the Free Officers' coup represented a revolution, marking the start of widespread change in the socio-economic and political nature of Libya. He proclaimed that the revolution meant "freedom, socialism, and unity", and soon implemented measures to achieve this.
=== Appellate reversal === On October 24, 2011, the United States Court of Appeals for the Second Circuit ruled in favor of Banki and reversed the sanctions charges against him. Judge Keenan's court-ordered Banki's release 10 days later on November 2, 2011. The appellate court ruled that Judge John F. Keenan had erred at trial; in denying Banki's defense request to instruct the jury on the law that specifically exempts family money as an exception to the sanctions law, permitting such transfers without the need for a license. The final appellate court brief stated: "Banki's conviction [on the sanctions charges] cannot stand". Prosecutors reopened the case to pursue a retrial in February 2012. However, after a few months of delay and the assignment of a new judge, the case was closed criminally with no option for future civil or criminal prosecution. Rather than pay for the high cost of a second criminal defense trial, Banki agreed to relinquish $710k of his assets. In exchange, prosecutors agreed that Banki was not guilty of the sanctions charges without going through a second trial and that they would end pursuing the case further in criminal or civil courts. The case was permanently closed on July 24, 2012. In the final court hearing, Banki's prison record was cleared. During the hearing, Banki said he had lived through "the darkest hours" of his life while in prison. "I watched my life pass me by. Those days will never be replaced". Judge Engelmayer in clearing Banki's prison record called him a "talented man, even brilliant". The judge also stated: ". . .
Sources: en.wikipedia.org
=== Classification === MSUD has five clinical phenotypes that are very distinct from one another. The most common and severe is the classical type with low residual activity from 0–2% of normal. Milder types include intermediate and intermittent with higher residual activities from 3–30% of the normal. Most unique is the thiamine-responsive type, where patients respond to high doses of thiamine administered, although this method is controversial. Lastly, the E-3 deficient type is correlated to combined enzyme deficiencies in pyruvate dehydrogenase, BCKD complexes, and alpha-ketoglutarate dehydrogenase, since E3 is common within mitochondrial alpha-ketoacid dehydrogenase complexes. NBS (newborn screening) detects most individuals with intermediate MSUD, but those who were not screened as newborns can be later diagnosed with MSUD. In these individuals, plasma BCAA concentrations are similar to those who have classic MSUD. However, they have better Lucine tolerance, and during acute metabolic decompensation episodes, they do not require intensive nutritional support. Severe metabolic intoxication with significant encephalopathy and leucinosis can occur if subjected to serious catabolic stress.
== Structure == The structure and properties of graphite oxide depend on the particular synthesis method and degree of oxidation. It typically preserves the layer structure of the parent graphite, but the layers are buckled and the interlayer spacing is about two times larger (~0.7 nm) than that of graphite. Strictly speaking "oxide" is an incorrect but historically established name. Besides epoxide groups (bridging oxygen atoms), other functional groups found experimentally are: carbonyl (C=O), hydroxyl (-OH), phenol and for graphite oxides prepared using sulphuric acid (e.g. Hummers method) some impurity of sulphur is often found, for example in a form of organosulfate groups. The detailed structure is still not understood due to the strong disorder and irregular packing of the layers. Graphene oxide layers are about 1.1 ± 0.2 nm thick. Scanning tunneling microscopy shows the presence of local regions where oxygen atoms are arranged in a rectangular pattern with lattice constant 0.27 nm × 0.41 nm. The edges of each layer are terminated with carboxyl and carbonyl groups. X-ray photoelectron spectroscopy shows the presence of several C1s peaks, their number and relative intensity depending on the particular oxidation method used. Assignment of these peaks to certain carbon functionalization types is somewhat uncertain and still under debate. For example, one interpretation goes as follows: non-oxygenated ring contexts (284.8 eV), C-O (286.2 eV), C=O (287.8 eV) and O-C=O (289.0 eV).
=== Resources created === CRAG: Computational resources for assembling genomes (CRAG) was created to assist users in assembling of genomes from short read sequencing (SRS). CRAG pursues the following major objectives: Collection and compilation of computation resources Brief description of genome assemblers Maintaining SRS and related data Service to community to assemble their genomes CRIP: Computational resources for predicting protein–macromolecular interactions (CRIP) was developed to provide resources related to interaction. This site maintains a large number of resources on the interaction of proteins that includes protein–protein, protein–DNA, protein–ligand, protein–RNA. BioTherapy: Bioinformatics for Therapeutic Peptides and Proteins (BioTherapi) was developed for researchers working in the field of protein/peptide therapeutics. The platform was created to provide a single platform for this area of research. This site includes relevant information about the use of peptides/proteins in drugs and synthesis of new peptides. It also covers problems in their formulation, synthesis and delivery processes. HIVbio: HIV Bioinformatics (HIVbio) site contains various types of information on Human Immunodeficiency Virus (HIV) life cycle and Infection.
=== Roman era === In the 1st century BC, the Romans founded Augusta Taurinorum. Via Garibaldi traces the exact path of the Roman city's decumanus which began at the Porta Decumani, later incorporated into the Castello or Palazzo Madama. The Porta Palatina, on the north side of the current city centre, is still preserved in a park near the cathedral. Remains of the Roman-period theatre are preserved in the area of the Manica Nuova. Turin reached about 5,000 inhabitants at the time, all living inside the high city walls.
=== 20 December === President Putin stated that the situation was "extremely difficult" in the four areas of Russia-annexed Ukraine. Putin ordered the Federal Security Services to step up surveillance at the country's borders to combat "emergence of new threats" from abroad and traitors. President Zelenskyy visited the Bakhmut region. Russian energy exporter Gazprom said that despite a fatal explosion at the Urengoy–Pomary–Uzhhorod pipeline they were able to supply gas to their customers using parallel pipelines without any shortages.
Sources: en.wikipedia.org
Hematocrit measurements had previously been described in the literature, but Wintrobe's method differed in that it used a large tube that could be mass-produced to precise specifications, with a built-in scale. The fraction of red blood cells in the tube was measured after centrifugation to determine the hematocrit. The invention of a reproducible method for determining hematocrit values allowed Wintrobe to define the red blood cell indices.
Esters can be directly converted to nitriles. Methyl esters are often susceptible to decarboxylation in the Krapcho decarboxylation. Phenyl esters react to hydroxyarylketones in the Fries rearrangement. Specific esters are functionalized with an α-hydroxyl group in the Chan rearrangement. Esters with β-hydrogen atoms can be converted to alkenes in ester pyrolysis. Pairs of esters are coupled to give α-hydroxyketones in the acyloin condensation.
=== 3D printing === In 2017, scientists from Chalmers University of Technology in Sweden demonstrated cartilage tissue engineering using 3D bioprinting. They used two different bioinks with nanofibrillated cellulose (NFC) to conduct the tests: NFC with alginate (NFC/A) and hyaluronic acid (NFC/HA). The bioinks were co-printed with irradiated human chondrocytes [8]. The team had success with NFC/A. In September 2021, researchers created cartilage repair implants utilizing a process of three-dimensional weaving to combine artificial materials with stem cells. The bioartificial implants are designed to partly dissolve over time, leaving only natural tissues in the repaired joints. As of October 2021, scientists have seen success in treating dogs but further research is required before the technique could move to clinical trials for humans. Also in September 2021, scientists from the Nakayama Lab at Saga University and Kyoto University in Japan fabricated 3D printed cartilage constructs from stem cells.
== Collagen and accessory proteins == Almost all of the organic (non-mineral) component of bone is dense collagen type I, which forms dense crosslinked ropes that give bone its tensile strength. By mechanisms still unclear, osteoblasts secrete layers of oriented collagen, with the layers parallel to the long axis of the bone alternating with layers at right angles to the long axis of the bone every few micrometers. Defects in collagen type I cause the commonest inherited disorder of bone, called osteogenesis imperfecta. Minor, but important, amounts of small proteins, including osteocalcin and osteopontin, are secreted in bone's organic matrix. Osteocalcin is not expressed at significant concentrations except in bone, and thus osteocalcin is a specific marker for bone matrix synthesis. These proteins link organic and mineral component of bone matrix. The proteins are necessary for maximal matrix strength due to their intermediate localization between mineral and collagen. However, in mice where expression of osteocalcin or osteopontin was eliminated by targeted disruption of the respective genes (knockout mice), accumulation of mineral was not notably affected, indicating that organization of matrix is not significantly related to mineral transport.
Sources: en.wikipedia.org
It binds the growth hormone-releasing hormone receptor on pituitary somatotroph cells. Receptor activation raises cyclic AMP and promotes release of stored growth hormone granules. Because the peptide persists longer than natural releasing hormone, stimulation is prolonged rather than brief.
The drug affinity complex links the peptide to serum albumin through a covalent bond. The conjugate is too large to be filtered quickly by the kidneys and is shielded from enzymatic breakdown. This extends the apparent half-life from roughly minutes to several days.
Long-term safety and any clinical benefit are unestablished. Published human data cover small groups over limited periods and focus on hormone levels rather than health outcomes. Whether prolonged elevation of growth hormone and insulin-like growth factor 1 is beneficial or harmful is an open question.
The mass difference from the linker is large enough for routine detection by mass spectrometry. The unconjugated form gives a single sharp signal at its expected weight. Material that has already reacted with albumin shows a much higher mass and a broadened chromatographic peak.