A practical reference on imidazole coordination: what it is, how it behaves, what the literature reports, and where the honest uncertainties sit.
This page was last updated on 2026-01-18 and is reviewed periodically as new material appears.
GHK-Cu is a coordination complex formed between the tripeptide glycyl-L-histidyl-L-lysine and a copper(II) ion. The peptide backbone consists of glycine, histidine, and lysine joined in that order. Copper is held through the imidazole nitrogen of histidine and the alpha-amino group at the N-terminus, which together produce a square-planar arrangement around the metal center. The solid appears blue to violet, a color that originates from d-d electronic transitions within the copper coordination sphere. The complex is indexed under CAS number 89030-95-5.
The sequence now called GHK was first reported in the early 1970s after isolation from human plasma, where it was noted to influence liver cell behavior in laboratory preparations. Later work described a copper-binding form and its activity in fibroblast and wound-model experiments. Review articles frequently group the substance with other copper peptides. Concentrations in blood appear to fall with age in several small surveys, although the reason for this trend is not settled. Whether such a decline carries functional consequences remains an open question.
Published work on GHK-Cu concentrates largely on cell culture systems rather than whole organisms. Frequently used endpoints include collagen synthesis, expression of matrix metalloproteinases, and migration of fibroblasts. Some reports describe antioxidant behavior, while others stress delivery of copper into cells. These mechanisms are proposed rather than demonstrated, and the relative weight of each pathway is unclear. Human trials are few and generally small, so laboratory findings should not be read as confirmed clinical results.
Proposed mechanisms for copper peptide activity center on delivery of copper ions to cells and on peptide fragments acting as signaling molecules. Copper is a cofactor for enzymes involved in collagen cross-linking and antioxidant defense, and the peptide may improve its availability at target sites. Separately, the tripeptide and its breakdown products have been reported to influence gene expression in cultured fibroblasts. Much of this evidence comes from laboratory cell cultures and animal models rather than controlled human trials. The relative contribution of the copper ion and the peptide sequence is therefore not fully settled.
Stability depends on temperature, light exposure, moisture, and the presence of oxidizing or reducing agents. Solid material held dry and protected from light is generally more stable than aqueous solutions, which can undergo gradual degradation. Recommended storage in much of the literature is a freezer at around minus twenty degrees Celsius for long-term retention, with working aliquots kept cold and shielded from light. Repeated freeze-thaw cycles and alkaline pH are commonly noted as factors that accelerate loss of the intact complex, though exact degradation rates vary.
| Property | Value | Notes |
|---|---|---|
| Chemical class | Copper(II) peptide complex | Peptide chain coordinated to a single metal ion |
| CAS number | 89030-95-5 | Indexed for the peptide-copper complex |
| Molecular formula | C14H22CuN6O4 | Approximate formula for a one-to-one complex |
| Appearance | Blue to violet solid | Color from copper d-d transitions |
| Solubility class | Freely soluble in water | Also dispersible in some polar solvents |
GHK-Cu is a coordination complex formed from the tripeptide glycyl-L-histidyl-L-lysine and a copper(II) ion. The peptide binds copper through its histidine imidazole nitrogen, the terminal amino group, and the deprotonated amide nitrogen. This arrangement creates a square-planar or distorted geometry around the metal center, depending on pH and the presence of competing ligands. The complex occurs naturally in human plasma, saliva, and urine at low concentrations, and its sequence is conserved across many vertebrate species.
Discovery of GHK is generally attributed to work in the 1970s that isolated a plasma factor influencing liver cell behavior. Subsequent studies identified the copper-binding tripeptide and its ability to chelate copper with high affinity. Early reports linked the complex to wound healing and tissue remodeling in animal models. The free peptide and the copper-bound form have different properties, so the two are distinguished in the literature. Whether endogenous GHK-Cu serves a single primary physiological role remains an open question.
GHK-Cu is the copper(II) complex of the tripeptide glycyl-L-histidyl-L-lysine, a short sequence of three amino acids. The peptide was first isolated from human plasma in 1973 during research on factors that influence tissue repair in liver. Its ability to bind copper ions became a central point of interest because the metal changes the peptide's chemistry and its behaviour in laboratory systems. Today the compound appears in cosmetic formulations, cell-culture studies, and biochemistry literature under several names.
The peptide sequence places a histidine in the middle, and this residue dominates metal binding. Copper(II) coordinates through the imidazole nitrogen of histidine and the terminal amino group, forming a stable chelate ring system. Loss of the copper ion leaves the free tripeptide, which has different solubility and reactivity. This structural detail matters because assays that measure only the peptide backbone can miss whether copper is still bound to it.
Aqueous solutions of GHK-Cu are less stable than the dry powder. The peptide backbone is vulnerable to hydrolysis at extreme pH, and copper can be stripped from the complex by strong chelating agents such as EDTA or citrate. Oxidising agents and high concentrations of ascorbic acid can reduce copper(II) and change the complex, which is one reason formulators often keep such ingredients in separate phases. How quickly these changes occur under real storage conditions depends on pH, buffer, temperature and packaging, and quantitative data on the subject are limited.
Dry material is normally held cold, commonly at -20 °C for long-term storage and 2 to 8 °C for working quantities, protected from light and moisture. Vials should be allowed to reach room temperature before opening so that condensation does not form on the powder. In liquid formulations the complex is generally kept near neutral to slightly acidic pH, because strongly alkaline conditions favour precipitation of copper hydroxide. Antioxidants or chelate-stabilising excipients are often added, though the specific approaches are proprietary and rarely published in detail.
These brands are labeled as "grain-free" and list peas, lentils, or potatoes as the main ingredient. The top three brands associated with reports of cardiomyopathy are Acana with 67 reports, Zignature with 64, and Taste of the Wild with 53 reports. In 2022, the FDA released a follow-up report which superseded the 2019 research. The follow-up report stated the following:
Global Positioning System (GPS) – The most widely used satellite navigation system, maintained by the US Air Force, which uses a constellation of 31 satellites in low Earth orbit. The orbits of the satellites are distributed so at any time at least four satellites are above the horizon over each point on Earth. Each satellite has an onboard atomic clock and transmits a continuous radio signal containing a precise time signal as well as its current position. Two frequencies are used, 1.2276 and 1.57542 GHz. Since the velocity of radio waves is virtually constant, the delay of the radio signal from a satellite is proportional to the distance of the receiver from the satellite. By receiving the signals from at least four satellites a GPS receiver can calculate its position on Earth by comparing the arrival time of the radio signals. Since each satellite's position is known precisely at any given time, from the delay the position of the receiver can be calculated by a microprocessor in the receiver. The position can be displayed as latitude and longitude, or as a marker on an electronic map. GPS receivers are incorporated in almost all cellphones and in vehicles such as automobiles, aircraft, and ships, and are used to guide drones, missiles, cruise missiles, and even artillery shells to their target, and handheld GPS receivers are produced for hikers and the military. Radio beacon – a fixed location terrestrial radio transmitter which transmits a continuous radio signal used by aircraft and ships for navigation.
== See also == 2026 state visit by Donald Trump to China 2026 G20 Miami summit China–United States relations List of international trips made by Xi Jinping APEC China 2026 List of international presidential trips made by Donald Trump
Sources: en.wikipedia.org
Currently, there are 10 ACE inhibitors approved for use in the United States by the FDA: captopril (1981), enalapril (1985), lisinopril (1987), benazepril (1991), fosinopril (1991), quinapril (1991), ramipril (1991), perindopril (1993), moexipril (1995) and trandolapril (1996). ACE inhibitors are easily identifiable by their common suffix, '-pril'. ACE inhibitors can be divided into three groups based on their molecular structure of the enzyme binding sites (sulfhydryl, phosphinyl, carboxyl) to the active center of ACE: Alacepril Captopril (trade name Capoten), the first ACE inhibitor. Zofenopril These agents appear to show antioxidative properties but may be involved in adverse events such as skin eruptions. This is the largest group, including:
DNA binding site prediction on protein DNA the Double Helix Game From the official Nobel Prize web site DNA under electron microscope Dolan DNA Learning Center Double Helix: 50 years of DNA, Nature Proteopedia DNA Proteopedia Forms_of_DNA ENCODE threads explorer ENCODE home page at Nature Double Helix 1953–2003 National Centre for Biotechnology Education Genetic Education Modules for Teachers – DNA from the Beginning Study Guide PDB Molecule of the Month DNA "Clue to chemistry of heredity found". The New York Times, June 1953. First American newspaper coverage of the discovery of the DNA structure DNA from the Beginning Another DNA Learning Center site on DNA, genes, and heredity from Mendel to the human genome project. The Register of Francis Crick Personal Papers 1938 – 2007 at Mandeville Special Collections Library, University of California, San Diego Seven-page, handwritten letter that Crick sent to his 12-year-old son Michael in 1953 describing the structure of DNA. See Crick's medal goes under the hammer, Nature, 5 April 2013.
== Interactions == Protease inhibitors, nefazodone, sertraline, grapefruit, fluoxetine, erythromycin, diltiazem, and clarithromycin inhibit the metabolism of midazolam, leading to a prolonged action. St John's wort, rifapentine, rifampin, rifabutin, and phenytoin enhance the metabolism of midazolam leading to a reduced action. Sedating antidepressants, antiepileptic drugs (e.g., phenobarbital, phenytoin, and carbamazepine), first-generation antihistamines, opioids, antipsychotics, and alcohol enhance the sedative effects of midazolam. Midazolam is metabolized almost completely by cytochrome P450-3A4. Atorvastatin administration along with midazolam results in a reduced elimination rate of midazolam. St John's wort decreases the blood levels of midazolam. Grapefruit juice reduces intestinal 3A4 and results in less metabolism and higher plasma concentrations.
Sources: en.wikipedia.org
It is the copper complex of the tripeptide glycyl-L-histidyl-lysine. The metal ion is held by the histidine imidazole group and the peptide N-terminus. Most research on it concerns skin and wound models.
The tripeptide was first isolated from human plasma and has also been reported in saliva and urine. Plasma levels appear to decline with age in some small studies. Those observations rest on limited sample sizes.
It is not authorized as a systemic medicine in most countries. Cosmetic preparations list it as an ingredient rather than an active pharmaceutical substance. Legal status therefore differs by jurisdiction.
Freezer temperatures are common for long-term retention. Light and moisture exposure should be limited. Working portions are best kept cold and used without repeated freeze-thaw cycles.