GHK-Cu copper peptide

GHK-Cu copper peptide, in specification terms

Three amino acids and one metal ion. Glycine, L-histidine and L-lysine in that order, written Gly-His-Lys, holding a single copper(II) ion. The molecular formula is C14H24N6O4 with Cu, the molecular weight 403.94 g/mol, and the complex is registered under CAS 89030-95-5.

It is supplied as a deep blue lyophilised powder, readily soluble in water, stored at −20°C for the long term and 2 to 8°C in use. Vial sizes are 50mg and 100mg, and the GHK-Cu vials in this catalogue were released at 99.86% purity by HPLC on the current lot.

Three residues is short. BPC-157 and TB-500 are both longer chains, and both are simpler products than this one. What complicates a GHK-Cu copper peptide vial is not the length of the chain. It is the metal held inside it, which has to be accounted for in the handling, in the assay and in the mass printed on the label.

The name it carries depends on who is writing. In a research catalogue it is GHK-Cu. On a cosmetic ingredient list it is Copper Tripeptide-1, which is an INCI designation rather than a chemical one. In a registry it is CAS 89030-95-5. In a paper it may be glycyl-L-histidyl-L-lysine copper(II). Four names, one substance, and only the CAS number is unambiguous, which is why a certificate names it.

The free peptide and the GHK-Cu copper peptide are different substances

GHK and GHK-Cu are written almost everywhere as though they were one thing with an optional suffix. They are not. GHK is a colourless tripeptide. GHK-Cu is a coordination complex with its own formula, its own mass and its own CAS registration. The three amino acids are common to both. The substance is not.

The two sets of numbers are the quickest way to see it. Sixty-three and a half grams per mole separates them, which is one copper atom, and that atom is not an impurity or an additive. It is a constituent. A certificate that reports one substance while the vial holds the other is not a certificate of anything.

The colour is the clearest way to tell them apart in practice, and it is not cosmetic. A copper(II) ion surrounded by donor atoms absorbs part of the visible spectrum, and which part it absorbs depends on the atoms doing the surrounding. That is why copper(II) compounds are coloured at all, and why the shade moves when the ligands change. A colourless solution of the free tripeptide turns blue when copper(II) is introduced, because the complex has formed. The colour is the reaction reporting on itself.

So the blue cake in a GHK-Cu vial is evidence rather than decoration. Material sold as a GHK-Cu copper peptide that arrives white is GHK, whatever the label says. Material that arrives pale, patchy or green is a question worth putting to the supplier before it goes near an experiment. Nothing else in this catalogue offers a check that can be made by eye; the lyophilized powder every other vial here holds is white, and one white cake looks exactly like another.

Why two different formulae are printed for the same complex

Look the GHK-Cu copper peptide up in three places and you may get three formulae. This catalogue writes C14H24N6O4 with Cu at 403.94 g/mol. Public chemical reference pages commonly write C14H22CuN6O4, which comes out at about 401.91 g/mol. The difference is two hydrogen atoms, roughly 2.03 g/mol, and it is not a typographical error in either direction.

It is a difference of convention, and the convention encodes a piece of chemistry. The first form sums the neutral tripeptide and the copper atom and leaves the coordination implicit: this much peptide, plus this much metal. The second describes the coordinated species itself, in which two protons have been displaced from the ligand when the metal bound to it. Both refer to the same material. One is written as an inventory, the other as a structure.

Which matters in exactly one situation: when a number on a certificate is being compared with a number from somewhere else. Two figures a couple of grams per mole apart look like a discrepancy and are not one. A figure sixty-three grams per mole apart is a discrepancy, because that is the metal. Knowing which convention a document uses is the difference between reading a certificate and second-guessing it.

It is also the reason identity is settled by mass spectrometry against a reference standard rather than by comparing formula strings. A formula written two ways is still one substance; LC-MS reports what is actually there. That is the logic behind every identity line in the certificate of analysis library, and it is set out at more length in the guide to reading a peptide certificate of analysis.

What the histidine is doing

A tripeptide is not, as a rule, a copper ligand. The GHK-Cu copper peptide is one, and the reason sits in the middle residue.

Histidine carries an imidazole ring on its side chain, and imidazole nitrogen is one of the donor atoms that copper sites in proteins are commonly built from. Put a histidine in the second position of a very short chain, next to a free N-terminal amine, and the chain can fold around a single ion and present several nitrogen donors from the same molecule.

The donor set usually described for this complex comes from the glycine end and from the histidine: the terminal amine, the backbone amide nitrogen between the first two residues, and the imidazole nitrogen of the histidine side chain. Holding a metal with several donors from one molecule is chelation, and it is what allows the complex to be treated as a discrete substance that can be weighed, filled and stored rather than separating back into a peptide and a copper salt.

The lysine sits outside that set. Its side-chain amine is left free and charged, which is consistent with a complex recorded as readily soluble in water. Each of the three residues occupies a different position, and the order is not interchangeable: the same three amino acids in another arrangement would not be the same ligand.

Two things follow from that donor set, and neither appears on a label. The first is pH. Coordination through a backbone amide nitrogen requires that amide to give up its proton, and whether it does depends on the pH of whatever the complex is in. Copper-peptide complexes therefore have a pH window in which the species described above is the dominant one, and outside it the metal is held differently or not at all. A dry cake does not raise the question. A solution does, and the pH of that solution is part of the identity of what is in it rather than a detail of the container.

The second is that the literature rarely discusses this complex as a molecule on its own. Copper in blood plasma is carried very largely on serum albumin, which has a high-affinity copper site of its own at its N-terminus, and the work on GHK describes ternary arrangements involving peptide, metal and albumin together rather than a free complex moving about by itself. That is a description of copper chemistry in a biological medium. It is not a description of the material in a vial, which is a dry, characterised solid with a stated stoichiometry of one copper ion per tripeptide.

What the preclinical literature studies, and in what systems

A profile of a molecule has to say what has been looked at. It also has to say what kind of looking it was. Everything below is in-vitro and animal work on the GHK-Cu copper peptide, described as work that was done, in the systems it was done in. None of it describes an effect in a person, none of it is a reason to use this material for anything, and none of it is repeated here with an outcome attached. The material is supplied for in-vitro laboratory research only.

The coordination chemistry is the part of the literature that is genuinely about the molecule itself: copper(II) binding, the donor set, the stability of the complex, and its behaviour alongside albumin at physiological pH. That work is the reason the copper-bound form, rather than the free peptide, is the species most of the rest of the literature examines.

Beyond it sits a body of cell-culture and animal work in dermal and connective-tissue model systems. The vocabulary is worth having, because it is the vocabulary a reader will meet in the source papers and in every summary written from them. What follows is that vocabulary and nothing more.

Where GHK comes from, and how the vial is made

GHK is endogenous. It is a well-documented human tripeptide, found in plasma, and it was identified there rather than drawn on a bench. That sets it apart from most of this catalogue, where the compound is a synthetic chain corresponding to a region of a larger protein, as the BPC-157 vs TB-500 comparison sets out. GHK occurs as itself.

It was isolated in 1973 by Loren Pickart and Margaret Thaler, working on human plasma and reporting in Biochemical and Biophysical Research Communications. The tripeptide came out of work on liver cells in culture, as a plasma factor that altered how they behaved, and it was named for its sequence once that sequence was established. The copper-bound form was characterised later, through the 1980s, as the species the research examines. The history is unusually well documented for a three-residue peptide, and it is history rather than anything else: a date, a laboratory and a journal.

One figure from that literature is worth carrying, with its source attached and nothing concluded from it. Plasma GHK concentration is reported at roughly 200 ng/mL at around age twenty and roughly 80 ng/mL at around age sixty, a figure attributed to Pickart and repeated in the general reference literature. It is a property of the endogenous peptide in human plasma. It says nothing about the material in a vial, and no inference is drawn from it here.

None of which describes the material in a vial. Research-grade GHK-Cu copper peptide is manufactured, not extracted. Peptides of this kind are assembled by solid-phase synthesis, with the C-terminal residue anchored to a resin bead and the chain extended one residue at a time. The finished chain is cleaved from the resin, purified by preparative HPLC, complexed with a copper(II) source and lyophilised. The blue appears at the complexation step.

Short chains are the forgiving end of peptide synthesis. Coupling failures compound with length, and there is very little length here for them to compound over, which is part of why peptide purity figures at this end of the catalogue sit where they do. The difficulty in a copper peptide is not building the chain. It is controlling how much metal ends up bound to it, and then proving it.

Being endogenous changes nothing about how the material is supplied. The GHK-Cu copper peptide here is for in-vitro laboratory research only. That the sequence occurs in human plasma is a fact about the molecule and nothing more.

GHK-Cu copper peptide stability, oxidation and what a change of colour means

Storage for GHK-Cu is the same as for the rest of the catalogue: −20°C as a lyophilised powder for the long term, 2 to 8°C in use, and the general handling set out in how to store peptides. What the copper adds is not a different regime. It is a failure mode that can be seen.

Four things act on this complex, and all four are chemistry rather than housekeeping. pH, because the amide coordination described above depends on a proton having been given up, and a solution well outside the window in which that happens is not holding the metal the same way. Oxygen, because copper is redox-active and cycles between the two and one oxidation states, which is precisely why the antioxidant model-system literature exists and precisely why a reconstituted solution is a less stable object than a dry cake. Light, which drives that chemistry faster. And water, whether it arrives as residual moisture in a poorly sealed vial or as repeated freeze-thaw across a cake that keeps being taken out and put back.

Each of those shows up the same way. The colour is a direct readout of the copper's coordination environment, so anything that changes that environment changes the colour. A white peptide gives no such signal: it can degrade a long way before it looks any different. A blue one announces the problem through the glass.

The comparison to make is not against memory or against a photograph on a product page. It is against the appearance line on the certificate for that specific lot, which for every GHK-Cu lot we have released reads: blue lyophilised powder. That line is on the certificate for exactly this reason.

Solvent is a separate question from storage. The complex is recorded as readily soluble in water, and the blends built on it are recorded as soluble in bacteriostatic water; bacteriostatic water for peptides is covered in its own article, and the water itself is stocked separately. Nothing in this article is a preparation instruction.

Why the certificate has to account for the metal

For an ordinary peptide a certificate answers two questions. Is this the right molecule, which mass spectrometry settles, and how much of the material present is the target, which HPLC reports as a purity percentage. For a GHK-Cu copper peptide both are still necessary and neither is sufficient.

The problem is mass. A vial of lyophilised material weighs what it weighs, and that weight includes the copper, any counter-ion carried through from purification, and residual water. Trifluoroacetate is the usual counter-ion left by preparative HPLC. None of those is peptide. Some of it is not even optional: on the molecule itself, before any counter-ion or moisture is counted, the copper is 63.55 g/mol of 403.94, which is 15.7% of the mass of the complex. So a third figure is required: net peptide content, measured for that lot, stating how much peptide the vial actually holds. Most of reading a peptide certificate of analysis is finding that line and checking it against the fill.

It is worth being precise about what that figure is not. It is not the fill weight minus a fixed correction. The number on the label is a nominal fill, and across the eight GHK-Cu lots in the certificate library the measured content lands both under and over it: 94.85mg and 95.56mg on 100mg fills, 109.135mg on another, 47.11mg and 65.80mg on 50mg fills. That spread is the argument for measuring each lot rather than publishing a single figure and reusing it. A supplier quoting one content number for a product rather than one per lot is quoting something that was true of a batch that has since been sold.

How that figure is arrived at is worth one sentence, because it is the line on a certificate most often read as though it were free. Net peptide content is a measurement in its own right, established by quantifying the peptide against a reference standard rather than calculated from the purity percentage. Amino-acid analysis after hydrolysis and quantitative HPLC against a characterised standard are the usual routes. Purity is a proportion of what was detected. Content is an amount. A certificate that reports only the first has not measured the second.

Handling follows from the same chemistry, and the certificate carries the reference point for it. The appearance recorded on every lot we have released is blue lyophilised powder, and that line is what a cake should be compared against.

Every GHK-Cu copper peptide lot released, and what its certificate says

Eight lots of GHK-Cu have been released and every one of them has a certificate published against its lot number, including lots that sold out months ago. Identity on all eight is recorded as confirmed by LC-MS, and all eight were assayed by Freedom Diagnostics, an independent laboratory, with the appearance recorded in each case as blue lyophilised powder.

The table is the argument for lot-level publication, made without a word of argument. Purity across the eight runs from 99.538% to 99.95% against a ≥99% specification, a narrow band, and still eight different numbers. Net peptide content varies more, and in both directions against the nominal fill. Neither column could be replaced by a single figure on a product page without the figure being wrong for seven lots out of eight.

Which is also the reason a certificate is looked up rather than trusted. The number printed on the vial in front of you is the only one that matters, and entering that lot number returns the certificate for that batch rather than the most flattering one on file.

Research powder and cosmetic serum are different material states

Most people typing this molecule's name into a search box are looking at a bottle of serum, not a vial of powder. It is worth being direct about the difference, because the two are documented under different systems and the vocabulary does not carry across.

A cosmetic product names its ingredients under INCI, the international nomenclature used on ingredient lists, where this complex is Copper Tripeptide-1. That name identifies an ingredient in a formulation. It carries no purity figure, no lot number, no identity confirmation and no measured content, because an ingredient list is not an analytical document and was never meant to be one. A research vial is documented the other way round: one substance, one lot, one certificate, with HPLC purity, LC-MS identity and measured net peptide content attached to a number printed on the label. Neither system is a deficient version of the other. They answer different questions.

The material state differs too. What this catalogue supplies is a dry lyophilised GHK-Cu copper peptide cake in a sealed vial, stored at −20°C, for in-vitro laboratory research only. It is not a cosmetic, it is not formulated, and nothing in this article describes preparing or applying it to anything.

The units are where the confusion usually starts, so here is the arithmetic. Concentrations on consumer labels are often given in parts per million: 10,000 ppm is 1% by weight, so a label reading 2,400 ppm is 0.24% by weight, or 2.4mg of the ingredient per gram of product. For a dilute aqueous solution, where a millilitre weighs roughly a gram, 1mg per mL works out at roughly 1,000 ppm. That is unit conversion and nothing else. It is not a recommendation about any concentration, and the material described on this page is supplied as dry powder by the milligram rather than as a solution.

Copper ingredients that are not copper peptides

The phrase almost everyone writes is plural: copper peptides. The plural does real work, because the category it names is wider than this one complex and several things sold under a copper heading contain no peptide at all. The distinction is chemical and it is easy to state.

What separates them is how the metal is held. In a salt, a copper(II) ion is paired with a counter-ion and the two come apart in water; nothing is built around the metal. In a chelate, a single molecule wraps the ion and offers it several donor atoms at once, and the result behaves as one substance that can be weighed, filled and assayed. The GHK-Cu copper peptide is the second kind. Most of the copper on a cosmetic ingredient list is the first.

That difference decides what a document has to say. A certificate for a copper salt reports an assay of the salt, and there is no peptide in it to purify or count. A certificate for a copper peptide has to do three jobs: confirm the chain, measure how much of the material detected is that chain, and state how much peptide the vial actually holds with the metal accounted for. A supplier that cannot tell you which of those it has measured is a supplier worth reading about in the guide to vetting a research peptide supplier.

Where the GHK-Cu copper peptide sits across the catalogue

The GHK-Cu copper peptide is sold on its own in 50mg and 100mg vials, and it is the largest component by mass of both research blends. In the GLOW blend it is 50mg of a 70mg fill, which is 71% of the cake. In the KLOW blend it is 50mg of 80mg, which is 63%. The rest of GLOW is BPC-157 and TB-500 at 10mg each, the same two compounds sold together as the Repair Reference Panel, and KLOW adds KPV on top of those.

That composition is the whole explanation for their colour. A blend of white peptides with a blue one at more than sixty per cent of the mass gives a blue cake. It is one of the few cases where the appearance of a multi-component product can be predicted from its formulation, and a GLOW or KLOW vial that arrives white is inconsistent with the label on it. What actually separates the two, as the GLOW vs KLOW comparison sets out, is what is added around that shared copper core.

It also raises the documentation stakes. A blend's certificate has to report each component separately, because a single purity percentage across three or four targets is not a measurement of any of them, and one of those components is a copper complex carrying its own content question. Both blends here are assayed per component and published against the lot, which is why a GLOW certificate lists a GHK-Cu figure, a BPC-157 figure and a thymosin figure rather than one number for the vial.

For anyone deciding which of the four to read about next, the profiles of the GLOW peptide and the KLOW peptide blends cover their own formulations in the same detail this page gives the copper complex.