Researchers discovered that the copper peptide GHK-Cu can form a ternary (three-way) complex with cis-urocanic acid, a molecule naturally found in skin, suggesting this complex may be partly responsible for both molecules' known biological effects.
Ternary complex at physiological concentrationsGHK, copper, and urocanic acid naturally coexist in skin and plasma at levels sufficient to form a three-way complex, suggesting this species exists in the body
What the researchers found
The study demonstrates that cis-urocanic acid, previously not known as a significant copper binder, can coordinate Cu(II) ions. More importantly, GHK and cis-urocanic acid can both bind to the same Cu(II) ion simultaneously, forming a ternary complex [GHK][Cu(II)][cis-urocanic acid].
Based on the natural concentrations of these three molecules in human tissues (particularly skin and plasma) and the binding affinities measured, the authors conclude that this ternary complex likely exists in the body and may be partly responsible for the biological effects previously attributed to GHK or urocanic acid individually.
Why it matters
GHK-Cu is widely used in skincare for its wound healing and anti-aging properties, but its exact mechanism isn't fully understood. If GHK-Cu naturally forms a ternary complex with urocanic acid in skin, this could change how we understand the peptide's biology — the active species in the body may not be simple GHK-Cu but a more complex molecular partnership.
How the study worked
Biophysical chemistry study using spectroscopic techniques. Copper binding was characterized using electron spin resonance (ESR) spectroscopy and circular dichroism (CD). Binding affinities were measured and compared to known physiological concentrations of GHK, copper, and urocanic acid in human tissues.
What this study cannot tell us
This is a chemistry study measuring binding interactions, not a biological study testing cellular or physiological effects. The authors infer physiological relevance from concentrations and affinities but did not directly demonstrate the ternary complex forming in living tissue. The biological consequences of the ternary complex versus simple GHK-Cu were not tested.
How to read the evidence
This is a biophysical chemistry study using spectroscopic methods. It provides strong evidence for the chemical interaction but does not test biological effects. It is mechanistic/foundational research.
When this study was published
Published in 2020, this is relatively recent work that adds new chemical understanding to the well-studied GHK-Cu peptide system.
The bigger picture
This study adds a new layer of complexity to GHK-Cu biology. Most research on GHK-Cu assumes a simple peptide-copper interaction, but the body's chemistry is more nuanced. The discovery of a physiologically relevant ternary complex suggests that the biological context — what other molecules are present alongside GHK-Cu — matters for its activity. This could influence how copper peptide formulations are designed.
Questions still open
- Does the ternary GHK-Cu-urocanic acid complex have different biological activity than GHK-Cu alone?
- Could adding urocanic acid to GHK-Cu skincare formulations enhance their effectiveness?
- Are there other small molecules in skin that form similar ternary complexes with GHK-Cu?
Common questions
What is GHK-Cu and why is it used in skincare?
What does it mean that GHK forms a 'ternary complex'?
Read the original research
Ternary Cu(II) Complex with GHK Peptide and Cis-Urocanic Acid as a Potential Physiologically Functional Copper Chelate.
International journal of molecular sciences, 21(17)
Citation
Bossak-Ahmad, Karolina; Wiśniewska, Marta D; Bal, Wojciech; Drew, Simon C; Frączyk, Tomasz. (2020). Ternary Cu(II) Complex with GHK Peptide and Cis-Urocanic Acid as a Potential Physiologically Functional Copper Chelate.. International journal of molecular sciences, 21(17). https://doi.org/10.3390/ijms21176190