Dear Valerie: How do you handle chelation in a product that you want to include a copper peptide in?  Just skip it?

–Cu Later

Dear Cu:

Of all the peptides available for use in personal care, I really like copper peptides (specifically copper tripeptide-1). Peptides can be biologically active molecules. It’s well-established in peer-reviewed literature that copper tripeptide-1 is not only of import in our body’s biological processes, it has value in pharmaceutical applications for wound healing and regeneration. No wonder it has such allure in skincare. I also like peptides in general because their efficacy occurs at quite low use levels, making them tolerable to skin. 

Copper tripeptide-1 is probably the most famous, and most studied. It’s also known by the moniker Cu-GHK because the copper is covalently bound through a coordination bond to the amino acids that comprise the tripeptide, glycine (G), histidine (H) and lysine (K).² (When I worked with peptides in graduate school—not the kind for personal care—I frequently had to use the one-letter abbreviations for the amino acids comprising peptides. Who knew that information would come in handy for something more fun!)

The copper in copper peptide is not freely floating around but rather exists strongly bound as a Cu2+ to the glycine and histidine residues of the peptide. This greatly increases the stability of the Cu-GHK complex, meaning it would not be easy to remove the copper ion.²

I understand you are concerned about using a chelating agent in a formulation with this peptide because the chelating agent may grab onto the copper, rendering the benefits of the peptide useless. Your concern is valid.

While it is not easy to remove the copper from the peptide, as its electrons are tied up with the protein, it is still positively charged. And chelating agents tend to be negatively charged ligands. They work by binding positively charged (and usually unbound) metals. As Paula Abdul sang, opposites attract. While copper is a poor leaving group, a poor old schlep like EDTA has a much stronger affinity for copper than copper for the peptide. Since the copper still bears a positive charge, there is still opportunity for an interaction. Therefore, I would skip the chelating agent out of an abundance of precaution. That is, unless you use a terrible chelating agent that has a lower affinity for copper than the copper for the peptide… but then, what’s the point? I try not to use chelating agents anyway, unless I must.

References

1. U.S. Food and Drug Administration. OTC Monograph M016: Skin Protectant Drug Products for Over-the-Counter Human Use. 24 Sept 2021. 2021, https://www.accessdata.fda.gov/drugsatfda_docs/omuf/OTCMonograph_M016SkinProtectantDrugProductsforOTCHumanUse09242021.pdf.
2. Pickart, Loren et al. “The human tripeptide GHK-Cu in prevention of oxidative stress and degenerative conditions of aging: implications for cognitive health.” Oxidative medicine and cellular longevity vol. 2012 (2012): 324832. doi:10.1155/2012/324832

Valerie George

askvalerie@icloud.com

Valerie George is a cosmetic chemist, science communicator, educator, leader, and avid proponent of transparency in the beauty industry. She works on the latest research in hair color and hair care at her company, Simply Formulas, and is the co-host of The Beauty Brains podcast. You can find her on Instagram at @cosmetic_chemist or showcasing her favorite ingredients to small brands and home formulators at simply-ingredients.com