Protective Functions of β-Alanyl-L-Histidine and Glycyl-L-Histidyl-L-Lysine Glycoconjugates and Copper in Concert

Compound: GHK Citation: Naletova I, Rizzarelli E. Antioxidants (Basel). 2025;14(12):1512. PubMed

Summary

This is a review article, not an original experiment. It covers two naturally occurring peptides: carnosine (β-alanyl-L-histidine) and GHK (glycyl-L-histidyl-L-lysine), which comes from the matricellular protein SPARC. The authors note that GHK’s low stability can undermine its antioxidant, anti-aggregating and anti-inflammatory properties. They review how linking GHK to hyaluronan (HAGHK), and carnosine to trehalose or hyaluronan, preserves these peptides’ protective and copper-related functions.

Key Findings

• HAGHK derivatives increase GHK’s stability and protect or delay degradation of the hyaluronan itself
• The glycoconjugates (TreCar, HACar, HAGHK) keep the copper-binding ability of the peptides alone
• The sugars boost the “Cu,Zn-superoxide dismutase-like” activity of the copper(II) complexes
• The conjugates act as copper ionophores, using Cu2+ from the culture medium to raise intracellular copper
• Higher intracellular copper stimulates copper-driven signaling that produces BDNF, BMP-2 (trophic factors) and VEGF (an angiogenic factor)
• The copper chaperones CCS and Atox-1 act as transcription factors in this signaling

Relevance to GHK

This review matters for GHK formulation. On its own, GHK is unstable. Attaching it to hyaluronan is one way to make it more stable while keeping its copper binding and copper-delivery behavior, which is the basis of GHK-Cu. The abstract describes chemistry and cell-culture findings. It reports no animal or human data, and the paper does not examine GHK’s genome-wide gene regulation.

PubMed

See Also

• Parent compound: GHK
• GHK-Cu