Copper Peptides and Short Signal Peptides

Copper peptides are tripeptides that chelate copper(II), GHK-Cu (glycyl-histidyl-lysine) being the best characterised; AHK-Cu substitutes alanine for glycine. Signal peptides are fragments of extracellular matrix proteins, often N-terminally palmitoylated to increase lipophilicity, such as palmitoyl pentapeptide-4 (Pal-KTTKS) and palmitoyl tripeptide-1 (Pal-GHK). Neurotransmitter-mimetic peptides such as acetyl hexapeptide-3 (argireline) and SNAP-8 reproduce a segment of SNAP-25 and are studied for competition within the SNARE complex.

These compounds are studied in fibroblast and keratinocyte culture by measuring gene expression (collagen, elastin and matrix metalloproteinase transcripts), protein secretion by ELISA, and, for the SNARE-mimetic peptides, vesicle exocytosis in neuronal cell lines. Melanocortin analogues sometimes listed beside them, such as Melanotan I and II, belong to a different receptor class and are covered in the melanocortin guide.

Identity is established by mass spectrometry: an intact mass, or a precursor and fragment transition (MRM) matched against a reference standard, confirms that the sequence in the vial is the one on the label. Purity is a chromatographic figure, the principal peak area by reversed-phase HPLC, and it bounds peptide-related impurities only; it says nothing about counterion, water or residual solvent content, which is why net peptide content is reported separately. Lyophilised material is stored cold, dry and dark, and a certificate states what was measured on one named lot. Copper complexes are blue rather than white, and the copper-to-peptide ratio, measured by ICP or UV-visible spectroscopy, is part of their identity. Palmitoylated peptides are poorly soluble in water and need an appropriate solvent before HPLC, and their intact mass must include the fatty-acid group.

Many studies of these peptides are formulation studies sponsored by ingredient manufacturers, small in size and run on a specific product rather than the isolated peptide. A result obtained with one vehicle does not transfer to another, and the hydrophilic peptides in this class are large relative to what passes intact stratum corneum in permeation models. Prefer independent cell-culture and permeation studies that report the peptide concentration actually tested.