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Cjc-1295 Structure And Mechanism — Worked Examples

By Editorial Desk · published 2026-06-28 · last reviewed 2026-07-19 · Topic

DAC raises a handful of sensible questions. This page answers them in order, starting with the fundamentals and moving to applications.

This page was last updated on 2026-07-19 and is reviewed periodically as new material appears.

CJC-1295 Structure And Mechanism

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.

Binding to GHRH receptors on pituitary somatotroph cells triggers cyclic AMP signaling and stimulates growth hormone synthesis and release. Because the peptide acts upstream of the pituitary, effects are mediated through endogenous growth hormone rather than direct receptor activation in peripheral tissues. Increases in insulin-like growth factor 1 are generally described as a downstream consequence. Most published human exposure data come from small early-stage studies, and the clinical significance of the pharmacokinetic profile remains incompletely characterized.

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.

Background and Molecular Design

CJC-1295 belongs to a family of synthetic peptides modeled on growth hormone-releasing hormone, the hypothalamic signal that prompts the pituitary to release growth hormone. The compound is built from the first twenty-nine amino acids of the natural human sequence, a fragment that retains full receptor binding capacity. Native growth hormone-releasing hormone is degraded quickly in circulation, so the fragment alone has limited practical value. Early work therefore focused on chemical modifications that preserve receptor binding while slowing enzymatic breakdown. The result is a molecule described in the literature as a long-acting analog of the natural hormone.

Two forms circulate under the CJC-1295 name, and they differ by a single appended group. The version without a drug affinity complex carries four substitutions along the peptide chain, including a D-alanine near the amino terminus and replacements at three other positions. These changes block the enzyme dipeptidyl peptidase IV and remove a methionine residue that is prone to oxidation. The modified fragment is frequently labeled MOD GRF 1-29. Naming conventions are inconsistent across informal sources, which is a common source of confusion.

The second form adds a maleimide-bearing linker to the lysine at the carboxyl end. This group reacts with cysteine-34 on circulating serum albumin, forming a covalent bond that keeps the peptide in the bloodstream for far longer. ConjuChem developed the molecule as a way to extend the action of a peptide without frequent administration. The albumin attachment is the defining structural feature of the drug affinity complex version. Whether continuous exposure produces effects distinct from shorter pulses remains an unresolved research question.

Cjc-1295 at a glance

PropertyValueNotes
Physical formLyophilized white powderSupplied as a freeze-dried solid for research use
Molecular weightApproximately 3,647 Da (DAC form)Lower for the variant lacking the albumin-binding moiety
SolubilitySoluble in water and aqueous bufferTypically dissolved in sterile or bacteriostatic water
Typical storage temperature−20 °C or belowDry powder, desiccated and protected from light
Common analytical methodReversed-phase HPLC with mass spectrometryUsed for purity estimation and identity confirmation

Structure And Receptor Pharmacology

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.

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Background and Receptor Mechanism

CJC-1295 is a synthetic peptide belonging to the growth hormone-releasing hormone analog family. It comprises twenty-nine amino acid residues derived from the N-terminal region of natural GHRH. The molecule incorporates several non-natural substitutions that increase resistance to enzymatic degradation. These modifications extend its activity compared with the native hormone fragment. Researchers use it to study pituitary growth hormone secretion in laboratory and clinical settings. This compound is distinct from native GHRH in its stability profile.

Two principal forms appear in the literature and in research supply. One carries a drug affinity complex, a maleimide-based group that forms a covalent bond with circulating albumin. This linkage slows clearance and produces a long-lasting elevation of peptide levels. The other form lacks that group and is often labeled MOD GRF(1-29). It has a much shorter circulation time. Both variants retain the same core receptor-binding sequence. Reported half-lives differ substantially between the two.

Molecular Background and Naming

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.

Notes from published material

== Biosynthesis == FAD plays a major role as an enzyme cofactor along with flavin mononucleotide, another molecule originating from riboflavin. Bacteria, fungi and plants can produce riboflavin, but other eukaryotes, such as humans, have lost the ability to make it. Therefore, humans must obtain riboflavin, also known as vitamin B2, from dietary sources. Riboflavin is generally ingested in the small intestine and then transported to cells via carrier proteins. Riboflavin kinase (EC 2.7.1.26) adds a phosphate group to riboflavin to produce flavin mononucleotide, and then FAD synthetase attaches an adenine nucleotide; both steps require ATP. Bacteria generally have one bi-functional enzyme, but archaea and eukaryotes usually employ two distinct enzymes. Current research indicates that distinct isoforms exist in the cytosol and mitochondria. It seems that FAD is synthesized in both locations and potentially transported where needed.

It is quite clear that the structure of the enzyme, to be specific the active site, is very important in understanding the mechanism of reaction. For this reason, Rees and colleagues studied the enzyme-ligand complex to get a clear answer for the role of the zinc ion. These studies found that, in free enzyme, the zinc coordination number is five; the metal center is coordinated with two imidazole Nδ1 nitrogens, the two carboxylate oxygens of glutamate-72, and a water molecule to form a distorted tetrahedral. However, once ligand binds at the active site of carboxypeptidase A, this coordination number can vary from five to six. When bound to dipeptide glycyl-L-tyrosine, the amino nitrogen of the dipeptide and the carbonyl oxygen replaced the water ligand. This would yield a coordination number of six for the zinc in the carboxypeptidase A- dipeptide glycyl-L-tyrosine complex. Electron density maps gave evidence that the amino nitrogen occupies a second position near glutamate-270. The closeness of these two residues would result in a steric hindrance preventing the water ligand from coordinating with zinc. This would result in a coordination number of five. Data for both are substantial, indicating that both situations occur naturally. There are two proposed mechanisms for the catalytic function of carboxypeptidase A. The first is a nucleophilic pathway involving a covalent acyl enzyme intermediate containing active site base Glu-270. Evidence for this anhydride intermediate is mixed; Suh and colleagues isolated what is assumed to by the acyl intermediate.

=== Some UN World Food Programme grants added back === On April 8, 2025, USAID announced it was making some exceptions to the recent announcement of cancelled participation in the UN's World Food Programme. Specifically, USAID was restoring food aid to Lebanon, Syria, Somalia, Jordan, Iraq and Ecuador, and other countries for a total of 14 nations (plus the International Organization for Migration in the Pacific region). However, food aid was not restored to Yemen or Afghanistan with a State Department spokesperson saying this was “based on concern that the funding was benefiting terrorist groups, including the Houthis and the Taliban.”

Sources: en.wikipedia.org

Further detail

== References == Aagaard et al.: "An inflammatory role for the mammalian carboxypeptidase inhibitor latexin: relationship to cystatins and the tumor suppressor TIG1." Structure 13(2), 309–317, 2005. Cho et al.: "Hypermethylation of CpG island loci and hypomethylation of LINE-1 and Alu repeats in prostate adenocarcinoma and their relationship to clinicopathological features." J Pathology 211(3), 269–277, 2007. Gautron et al.: "Ovacalyxin-32, a novel chicken eggshell matrix protein." J Biol Chem 276(42), 39243–39252, 2001. Jing et al.: "Tazarotene-Induced Gene 1 (TIG1) expression in prostate carcinomas and its relationship to tumorigenicity" J Natl Cancer Institute 94(7), 482–490, 2002. Liang et al.: "The quantitative trait gene latexin influences the size of the hematopoietic stem cell population in mice." Nature Genetics 39(2), 178–188, 2007. So et al.: "Multiple tumor suppressor genes are increasingly methylated with age in non-neoplastic gastric epithelia." Cancer Sci 97(11), 1155–1158, 2006.

==== Appointment and political stance ==== Thatcher was impressed by Heseltine's campaigning and love of headlines during the May 1979 election, in contrast to most of the Shadow Cabinet. After the Conservatives had won, and mindful of her earlier promise that he need not take on the Environment job in government, she offered him the Energy Department (an important job following the 1979 energy crisis caused by the Iranian Revolution). He preferred to be Secretary of State for the Environment after all, entering the Cabinet for the first time. During the macroeconomic disputes of the early 1980s, Heseltine was sometimes associated with the Cabinet "wets" (Peter Walker, Jim Prior, Ian Gilmour, Lord Carrington and Norman St John Stevas) but was not seen as one of them, nor was he invited to their private meetings. Both Nigel Lawson and Cecil Parkinson agreed in their memoirs (1992) that he accepted in principle the need to control public expenditure. He opposed the abolition of exchange controls in 1979 and opposed Geoffrey Howe's tight budget in 1981, suggesting a public sector pay freeze instead. Heseltine favoured privatisation of state owned industries, a novel idea in 1979 as the Conservatives were initially only proposing to denationalise the industries nationalised by Labour in the 1970s. Despite his initial reluctance to take on the job, Heseltine later described it as "four of the happiest years of my life". He passed the Wildlife and Countryside Act 1981, a conservation measure.

Dithiothreitol (DTT) is an organosulfur compound with the formula (CH(OH)CH2SH)2. A colorless compound, it is classified as a dithiol and a diol. DTT is redox reagent also known as Cleland's reagent, after W. Wallace Cleland. The reagent is commonly used in its racemic form. Its name derives from the four-carbon sugar, threose. DTT has an epimeric ('sister') compound, dithioerythritol (DTE).

Sources: en.wikipedia.org

Background from the literature

AntWiki – Bringing Ants to the World Wilson, Andrew (1878). "Ant" . Encyclopædia Britannica. Vol. II (9th ed.). pp. 94–100. AntWeb from The California Academy of Sciences Ant Species Fact Sheets from the National Pest Management Association on Argentine, Carpenter, Pharaoh, Odorous, and other ant species Ant Genera of the World – distribution maps The super-nettles. A dermatologist's guide to ants-in-the-plants

== See also == Family tree of German monarchs – he was related to every other ruler of Germany List of coupled cousins Austro-Hungarian entry into World War I Franc Jozeph Island, island in Albania named in honor of the Emperor. Order of St. George (Habsburg-Lorraine) Franz Josef Glacier was named after Emperor Franz Joseph I by the German geologist Julius von Haast in 1865.

=== Genome === The genome of Pseudomonas aeruginosa consists of a relatively large circular chromosome (5.5–6.8 Mb) that carries between 5,500 and 6,000 open reading frames, and sometimes plasmids of various sizes depending on the strain. Comparison of 389 genomes from different P. aeruginosa strains showed that just 17.5% is shared. This part of the genome is the P. aeruginosa core genome.

Sources: en.wikipedia.org

Frequently asked questions

How does CJC-1295 differ from modified GRF(1-29)?

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.

Is CJC-1295 an approved medicine?

It has not been approved by major regulatory agencies for any therapeutic indication. Material sold under this name is typically distributed for laboratory research only. Clinical use is not supported by large controlled trials.

What is known about its half-life?

Early human studies of the albumin-binding form reported circulation half-lives on the order of several days. The value depends on assay method and study design. Estimates for the form without the binding moiety are considerably shorter.

Is CJC-1295 the same as modified GRF(1-29)?

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.

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