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AHK-Cu
Technical Compound Reference | Orion Peptides Research Library
AHK-Cu is a copper-coordinated tripeptide formed from L-alanyl-L-histidyl-L-lysine (AHK) and copper(II). Its peptide sequence contains three residues: alanine, histidine, and lysine.
The compound belongs to the broader family of copper-binding peptides. Its chemical identity involves both the amino acid backbone and the coordination environment surrounding the copper ion.
AHK-Cu is structurally related to GHK-Cu. However, the two compounds differ at the first amino acid position. AHK contains alanine, whereas GHK contains glycine.
Although this substitution introduces only one additional carbon and two hydrogen atoms, it changes the peptide’s molecular composition and introduces an additional stereochemical center.
AHK-Cu is relevant to research involving metal–peptide coordination, ligand-binding equilibria, spectroscopic characterization, and analytical chemistry.
This reference examines its molecular identity, peptide structure, copper-binding chemistry, physicochemical characteristics, and laboratory identification methods.
1. AHK-Cu Chemical Reference
AHK-Cu should be identified using a defined chemical form. The free tripeptide and its copper complex have different molecular compositions.
| Property | Technical information |
|---|---|
| Compound name | AHK-Cu |
| Chemical designation | L-Alanyl-L-histidyl-L-lysine copper(II) complex |
| Alternative names | AHK copper peptide, Ala-His-Lys-Cu |
| Peptide sequence | Ala-His-Lys |
| One-letter sequence | AHK |
| Amino acid count | 3 |
| Metal ion | Copper(II), Cu²⁺ |
| Molecular category | Metallopeptide coordination complex |
| Common coordination motif | N-terminal amino group, peptide amide nitrogen and histidine imidazole |
| Free AHK CAS | 126828-32-8 |
| Free AHK formula | C₁₅H₂₆N₆O₄ |
| Free AHK molecular weight | Approximately 354.41 g/mol |
| Free AHK PubChem CID | 7408502 |
| AHK-Cu monohydrochloride CAS | 682809-81-0 |
| Registered monohydrochloride formula | C₁₅H₂₄ClCuN₆O₄⁻ |
| Registered monohydrochloride molecular weight | 451.39 g/mol |
| Monohydrochloride PubChem CID | 168431292 |
The molecular formula and molecular weight must always refer to the same chemical species.
Values assigned to the free peptide cannot be used as molecular specifications for a copper-bound form.
Likewise, the presence of hydrochloride or another counterion changes the overall material composition.
2. One Amino Acid Substitution Changes the Chemical Identity
The difference between AHK and GHK is located at the beginning of the peptide chain.
AHK contains:
Ala-His-Lys
GHK contains:
Gly-His-Lys
Histidine and lysine occupy the same positions in both sequences.
The only residue change is alanine replacing glycine.
Glycine vs Alanine
Glycine is the smallest amino acid.
Its side chain consists of one hydrogen atom.
Alanine has a methyl group attached to its alpha carbon.
This gives alanine a different molecular geometry and adds a stereochemical center absent from glycine.
Why Does This Small Change Matter?
Replacing glycine with alanine changes three features of the peptide.
Molecular composition
The alanine-containing peptide has one additional carbon atom and two additional hydrogen atoms relative to the glycine-containing peptide.
Backbone conformational freedom
Glycine can adopt a relatively broad range of backbone conformations.
Alanine has greater steric restriction because of its methyl group.
Stereochemistry
Alanine has a chiral alpha carbon.
Therefore, the L-configuration of the first residue forms part of the defined AHK structure.
These differences mean that AHK-Cu and GHK-Cu require separate chemical characterization.
3. Understanding the Three Residues
AHK contains two conventional peptide bonds connecting its three amino acids.
Its backbone can be represented as:
H-Ala-His-Lys-OH
The actual ionization state depends on the chemical environment.
Alanine: The N-Terminal Residue
Alanine occupies position 1.
Its N-terminal amino group is an important potential donor atom for copper coordination.
The methyl side chain influences local molecular geometry but is not itself a conventional copper-binding group.
Histidine: The Copper-Binding Anchor
Histidine occupies position 2.
Its side chain contains an imidazole ring with nitrogen atoms capable of coordinating transition-metal ions.
Histidine is therefore particularly important in metal-binding peptide chemistry.
The imidazole group helps create a coordination environment around copper.
Lysine: The C-Terminal Residue
Lysine occupies position 3.
It contains a basic amino group in its side chain and a terminal carboxyl group.
Both affect the peptide’s acid-base behavior.
The carboxylate group or lysine-associated donor atoms may contribute to certain metal-coordination arrangements depending on experimental conditions.
4. Copper Coordination: What Happens When AHK Meets Cu(II)?
Copper(II) can form coordination complexes with molecules containing suitable electron-donating atoms.
Nitrogen and oxygen atoms are common donors in peptide coordination chemistry.
AHK provides several possible donor sites.
The presence of the N-terminal amino group and histidine residue makes the peptide a plausible copper-binding ligand.
What Is a Ligand?
A ligand is a molecule or ion capable of coordinating to a central metal atom or ion.
In AHK-Cu, the AHK peptide acts as a ligand.
The copper ion serves as the metal center.
Possible Coordination Donors
Relevant donor groups include the N-terminal amino nitrogen, the histidine imidazole nitrogen and peptide-backbone nitrogen atoms.
Oxygen-containing groups may also influence coordination under particular conditions.
Related GHK-Cu research has characterized nitrogen-rich copper coordination arrangements.
However, the exact coordination environment of AHK-Cu should not be presented as experimentally identical to GHK-Cu without AHK-specific structural evidence.
Does AHK-Cu Have One Permanent Three-Dimensional Structure?
Not necessarily.
Metal coordination depends on chemical equilibria.
Changes in protonation, solvent composition or competing ligands can influence which molecular species are present.
A chemical drawing may represent one valid reference structure without describing every species present in solution.
5. Why pH Is Important in AHK-Cu Chemistry
A peptide’s metal-binding properties are affected by the ionization states of its functional groups.
The protonation of the histidine imidazole group, terminal amino group and other functional groups can change with pH.
These changes influence the peptide’s capacity to coordinate copper.
Protonation and Deprotonation
Protonation occurs when a chemical group gains a proton.
Deprotonation occurs when it loses a proton.
Some donor atoms become more available for coordination following deprotonation.
As a result, the preferred copper-binding arrangement may vary with pH.
Metal-to-Ligand Ratio
The amount of copper relative to AHK also matters.
A nominal 1:1 mixture contains equal molar quantities of the metal and peptide.
However, this does not automatically prove that all material exists exclusively as one 1:1 complex.
The distribution of species should be established using suitable analytical methods.
Competing Ligands
Other molecules in a solution may also bind copper.
Such competition can alter copper speciation.
Therefore, chemical compatibility cannot be predicted solely from the names of the substances present.
6. Copper Coordination Geometry and Electronic Properties
Copper(II) complexes often exhibit characteristic geometric and electronic behavior.
Their arrangement depends on the number and position of donor atoms around the metal.
For nitrogen-containing peptide ligands, distorted square-planar or square-pyramidal coordination environments may be relevant models.
However, a geometry established for a related copper peptide is not definitive proof of the same geometry in AHK-Cu.
Why Geometry Matters
Coordination geometry can influence the metal center’s electronic properties.
These characteristics affect spectroscopic measurements and redox behavior.
Why Are Many Copper Peptide Complexes Colored?
Copper(II) complexes can absorb visible light through transitions related to the electronic environment of the metal ion.
The resulting absorption profile may produce blue or violet coloration.
Appearance depends on the exact compound, concentration and chemical environment.
Color alone cannot establish identity, copper occupancy or purity.
Can Spectroscopy Investigate Copper Coordination?
Yes.
UV-visible spectroscopy and electron paramagnetic resonance can provide useful information about certain copper complexes.
Other methods may include circular dichroism, potentiometric measurements or structural analysis.
Each technique addresses a different aspect of the chemical system.
7. AHK-Cu and GHK-Cu: A Molecular Comparison
AHK-Cu is often compared with GHK-Cu because both contain histidine and lysine in positions 2 and 3.
Their first residues differ.
| Feature | AHK-Cu | GHK-Cu |
|---|---|---|
| Peptide sequence | Ala-His-Lys | Gly-His-Lys |
| First residue | Alanine | Glycine |
| Peptide length | 3 | 3 |
| Copper-binding element | Cu(II) | Cu(II) |
| Free peptide formula | C₁₅H₂₆N₆O₄ | C₁₄H₂₄N₆O₄ |
| Free peptide mass | ~354.41 g/mol | ~340.38 g/mol |
| First-residue chirality | L-Alanine is chiral | Glycine is achiral |
| Structurally identical | No | No |
Molecular Mass Difference
The free AHK tripeptide is approximately 14.03 Da heavier than free GHK.
This is consistent with the additional CH₂ unit introduced when glycine is replaced by alanine.
The same underlying composition difference is relevant when comparing equivalently defined copper complexes.
However, values for different salts or protonation states must not be directly compared as though they represent identical material forms.
Do Both Compounds Have Identical Copper Affinity?
That should not be assumed.
An amino acid substitution can influence metal-binding geometry and thermodynamics.
Directly comparable experimental measurements would be needed to establish the relative binding behavior under defined conditions.
Can Research Findings Be Transferred Between Them?
Not automatically.
Shared chemical features provide a basis for comparison.
They do not establish identical receptor interactions, cellular responses, or material stability.
8. What Has Been Studied Experimentally?
The AHK-Cu literature is substantially smaller than the literature available for GHK-Cu.
A frequently cited 2007 publication investigated the copper tripeptide using isolated follicle preparations and cultured dermal papilla cells.
The researchers measured experimental responses including cellular proliferation and selected apoptosis-related markers.
For a technical compound reference, the relevance of this study is its use of a chemically identified AHK-Cu preparation within a defined cell-based experimental system.
It does not establish the full copper coordination structure of every AHK-Cu material.
Direct and Indirect Molecular Evidence
A distinction should be made between three types of evidence.
Structural characterization examines molecular identity, chemical bonding and coordination.
Functional assays measure a defined cellular or biochemical response.
Mechanistic studies investigate the molecular interactions responsible for that response.
A functional assay does not automatically identify the direct binding target.
Likewise, research on GHK-Cu cannot substitute for direct structural or mechanistic testing of AHK-Cu.
9. Analytical Characterization of AHK-Cu
The analytical study of AHK-Cu presents two connected questions.
First, does the sample contain the expected Ala-His-Lys peptide?
Second, what copper-containing chemical species are present?
No single technique necessarily answers both questions completely.
Mass Spectrometry
Mass spectrometry provides molecular mass-to-charge information.
It can support identification of the AHK peptide and, where the method permits, copper-associated species.
However, the detected species depend on ionization and sample preparation.
Copper coordination may change during analysis.
For this reason, an observed peak should be assigned according to its exact proposed ionic structure.
HPLC
High-performance liquid chromatography can separate the peptide from certain impurities.
A suitable HPLC method provides information about chromatographic purity.
However, chromatographic conditions may disturb copper-binding equilibria.
Therefore, HPLC peak-area purity is not automatically a measurement of intact AHK-Cu coordination purity.
LC-MS
LC-MS combines chromatographic separation with mass analysis.
It can help assign molecular identities to separated components.
Additional methods may still be required to investigate copper-binding geometry.
ICP-MS
Inductively coupled plasma mass spectrometry is an elemental analysis technique.
It can quantify total copper in a sample.
However, total copper content is not the same as copper bound to AHK.
UV-Visible Spectroscopy
UV-visible absorption measurements can provide information about a copper complex’s optical behavior.
Changes in absorption may be associated with changes in coordination conditions.
A reliable interpretation requires suitable reference measurements.
EPR Spectroscopy
Electron paramagnetic resonance can investigate the electronic environment of Cu(II).
It is a useful technique for certain copper coordination complexes.
The resulting spectra can provide information complementary to mass spectrometry and elemental analysis.
Summary of Laboratory Methods
| Analytical method | Main question addressed |
|---|---|
| RP-HPLC | What components are separated and detected? |
| MS | Are the observed masses consistent with proposed species? |
| LC-MS/MS | What structural information can fragmentation provide? |
| ICP-MS | How much total copper is present? |
| UV-visible spectroscopy | What optical properties does the complex exhibit? |
| EPR | What is the Cu(II) electronic environment? |
| Potentiometric analysis | How does complex formation change with protonation? |
| Stability-indicating methods | What changes under defined conditions? |
A complete analytical program should be designed around the specific material and research objective.
10. Peptide Purity, Copper Content and Complex Identity
These three properties should be distinguished in any technical AHK-Cu reference.
Peptide Purity
Peptide purity describes the proportion of the intended peptide relative to certain detected peptide-related impurities.
Chromatographic methods are often used for this purpose.
Copper Content
Copper content describes the amount of copper present.
An elemental assay can provide this value.
Complex Identity
Complex identity describes the chemical association between the peptide and the copper ion.
This may require coordination-sensitive analytical techniques.
Why One Purity Percentage Is Not Enough
A sample may show a strong principal peptide chromatographic peak while containing an unexpected amount of copper.
A sample may also contain an appropriate total amount of copper while having a distribution of coordination species different from the intended reference.
Therefore, a single reported percentage does not describe every relevant quality attribute.
11. AHK-Cu Stability and Speciation
The stability of a copper tripeptide includes more than the integrity of its peptide bonds.
Researchers must consider both peptide chemistry and metal coordination.
Peptide Degradation
AHK contains two peptide bonds.
Under suitable conditions, chemical hydrolysis or other reactions may alter the peptide structure.
Ligand Exchange
Copper can interact with different ligands.
The distribution of copper species may change when other coordinating molecules are present.
Such changes do not necessarily require peptide bond cleavage.
Oxidation and Reduction
Copper can exist in more than one oxidation state.
The redox behavior of a copper complex depends on its ligand environment.
Specific redox activity should be established experimentally rather than assumed from the presence of copper.
Solid-State and Solution-State Behavior
A dried copper-peptide material may behave differently from the same material under solution conditions.
Moisture, pH, temperature, light, and surrounding chemical species can influence stability.
Storage duration should therefore be supported by studies conducted on the defined material.
12. What Should an AHK-Cu Certificate of Analysis Include?
A Certificate of Analysis records the testing performed on a particular batch.
For a copper-containing peptide, the most informative documentation goes beyond a single chromatographic purity value.
| COA field | Scientific purpose |
|---|---|
| Compound identity | Identifies the claimed material |
| Exact chemical form | Specifies the copper complex and any counterions |
| Peptide sequence | Identifies Ala-His-Lys |
| CAS number | Connects the material with the intended chemical reference |
| Batch number | Provides sample traceability |
| HPLC chromatogram | Shows chromatographic separation |
| Chromatographic purity | Reports a method-specific purity result |
| Mass spectrometry | Provides molecular identity-related evidence |
| Total copper assay | Quantifies copper, if tested |
| Copper-to-peptide ratio | Evaluates stoichiometry, if measured |
| Copper speciation | Describes coordination forms, if investigated |
| Water content | Reports residual moisture, if measured |
| Laboratory identity | Identifies the testing organization |
| Analytical date | Records when the analysis was performed |
Does HPLC Confirm AHK-Cu Identity?
HPLC provides separation-related information but cannot by itself establish every aspect of a copper coordination complex.
Complementary analytical methods may be required.
Does a Matching Molecular Mass Establish Copper Coordination?
It can provide useful evidence, but mass agreement alone does not determine the full coordination geometry or solution speciation.
Can Color Verify Copper Content?
No.
Visual appearance is not an accurate quantitative measurement of copper content or complex composition.
13. Frequently Asked Technical Questions
What is AHK-Cu?
AHK-Cu is a copper(II) coordination complex of the tripeptide alanine-histidine-lysine.
What does AHK stand for?
Alanine, histidine and lysine.
How many amino acids are in AHK-Cu?
Three.
What is the amino acid sequence?
Ala-His-Lys, abbreviated AHK.
What is the molecular formula of free AHK?
C₁₅H₂₆N₆O₄.
What is the molecular weight of free AHK?
Approximately 354.41 g/mol.
What is the commonly indexed CAS number of AHK-Cu?
682809-81-0 identifies a registered copper-complex monohydrochloride.
What is the molecular weight of AHK-Cu monohydrochloride?
451.39 g/mol for the specified PubChem reference form.
Does every AHK-Cu preparation have a molecular weight of 451.39 g/mol?
No. That value applies to a particular registered chemical form. Other defined coordination states or associated counterions can change the composition.
What metal does AHK-Cu contain?
Copper, generally represented in the +2 oxidation state.
Which amino acid is important for copper binding?
Histidine provides an important nitrogen-containing coordination site.
Why is the N-terminal residue important?
The N-terminal amino group can participate in metal coordination, while the first residue’s side chain influences molecular geometry.
Is AHK-Cu identical to GHK-Cu?
No. AHK-Cu contains alanine where GHK-Cu contains glycine.
What is the mass difference between free AHK and free GHK?
Approximately 14.03 Da.
Is AHK-Cu a cyclic peptide?
Its tripeptide backbone is linear. Copper coordination may constrain its geometry, but this is different from covalent backbone cyclization.
Does AHK-Cu contain a disulfide bridge?
No. The AHK sequence contains no cysteine residues.
Does AHK-Cu have one permanent solution structure?
Not necessarily. Copper coordination can depend on pH, stoichiometry and competing ligands.
Can HPLC determine AHK-Cu purity?
HPLC can provide chromatographic purity information under specified analytical conditions.
Can ICP-MS identify the peptide sequence?
No. ICP-MS measures elemental composition, including copper, rather than amino acid sequence.
Is copper content the same as copper occupancy?
No. Total copper measurement does not automatically establish how much copper is bound in the intended complex.
Can AHK-Cu undergo degradation?
Yes. The peptide and its coordination environment may undergo changes depending on chemical conditions.
Does AHK-Cu have a universal shelf life?
No. Stability information must apply to the exact material and formulation.
What is the main research challenge with AHK-Cu?
Distinguishing peptide identity, copper content, coordination chemistry, and functional experimental findings using appropriate analytical methods.
14. Scientific References
AHK-Cu Experimental Characterization
Pyo H.K. et al. (2007)
The Effect of Tripeptide-Copper Complex on Human Hair Growth In Vitro.
Journal: Archives of Pharmacal Research, 30, 834–839.
Technical relevance: AHK-Cu identification within controlled ex-vivo and cell-based experiments. The study concerns experimental responses rather than full chemical coordination characterization.
https://doi.org/10.1007/BF02978833
Free AHK Molecular Reference
PubChem: L-Alanyl-L-histidyl-L-lysine
CID: 7408502
Technical relevance: Tripeptide chemical identity, molecular structure and elemental composition.
https://pubchem.ncbi.nlm.nih.gov/compound/7408502
AHK-Cu Monohydrochloride Reference
PubChem: AHK-Cu
CID: 168431292
Technical relevance: Registered copper-complex chemical form, molecular formula, molecular weight and structural identifiers.
https://pubchem.ncbi.nlm.nih.gov/compound/168431292
Comparative Copper-Peptide Coordination Chemistry
Hureau C. et al. (2011)
X-ray and Solution Structures of CuII GHK and CuII DAHK Complexes: Influence on Their Redox Properties.
Journal: Chemistry – A European Journal.
Technical relevance: Structural techniques and copper-coordination principles for related peptide ligands.
https://doi.org/10.1002/chem.201100751
Note: This study concerns GHK and DAHK rather than AHK. Its findings provide comparative coordination chemistry, not direct structural proof for AHK-Cu.
Computational Copper Coordination Research
Alshammari N. and Platts J.A. (2020)
Theoretical Study of Copper Binding to GHK Peptide.
Journal: Computational Biology and Chemistry.
Technical relevance: Computational modeling, copper-binding geometry and molecular dynamics in a related copper tripeptide.
https://doi.org/10.1016/j.compbiolchem.2020.107265
Conclusion
AHK-Cu is a copper(II)-coordinated tripeptide based on the sequence Ala-His-Lys.
Its most important structural distinction from GHK-Cu is the substitution of alanine for glycine at the N-terminus.
Although the peptides share a histidine-containing copper-binding motif, they are separate chemical compounds.
AHK-Cu characterization requires careful attention to peptide sequence, stereochemistry, copper coordination, chemical form and molecular mass.
Laboratory methods such as HPLC, mass spectrometry, elemental copper analysis and spectroscopy provide complementary information.
A technically reliable AHK-Cu reference must distinguish between properties established for AHK-Cu itself and those inferred from related copper-peptide systems.
Technical research notice: This reference concerns molecular chemistry and analytical research. It does not provide instructions for dosing, administration, reconstitution or personal use. Chemical identification and batch testing do not establish that research material is suitable for human or veterinary applications.
