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PeptideAI
In vitro onlyskin

Palmitoyl Tripeptide-1

GHK with a fatty tail bolted on so it actually penetrates the stratum corneum — copper-peptide-style collagen signalling without the copper or the blue stain.

Also known as pal-GHK, Palmitoyl Oligopeptide, Biopeptide CL, Biopeptide CL

In vitro only — Cell or tissue studies. A mechanism, not yet an effect in a living body.

Strong fibroblast and explant data; human evidence comes almost entirely from studies of the blends it sits inside rather than the peptide on its own.

How it works

Palmitoyl tripeptide-1 is Gly-His-Lys with a C16 palmitic acid attached at the N-terminus. The lipid chain roughly reverses GHK's water-loving character, which is the single biggest obstacle to getting a small hydrophilic peptide through the lipid lamellae of the stratum corneum. Once in the dermis it behaves as a matrikine, increasing collagen I and IV, fibronectin, hyaluronic acid and glycosaminoglycan synthesis in fibroblasts. It does not carry copper, so the copper-dependent parts of the GHK-Cu story — the antioxidant enzyme induction, the wound-healing acceleration — do not automatically transfer. It is one of the two peptides in Matrixyl 3000 and one of the four actives in Haloxyl.

Targets: Dermal fibroblasts, Collagen I and IV, Fibronectin, Hyaluronic acid, Glycosaminoglycans

Dosing

ProtocolDoseFrequencyRoute
Standard leave-on serumNo timing constraints; compatible with vitamin C, unlike the copper form.—once or twice dailytopical
  • · Trade solutions run 2-5% of the finished formula; actual peptide is typically 50-200 ppm. From raw powder, 0.005-0.02% w/w.

Cycling

Continuous daily use.

Work out your exact syringe units →

Pharmacology

Half-life
Not established.
Onset
8-12 weeks of daily use.
Routes
topical
Molecule
Palmitoylated tripeptide (lipopeptide)
Sequence length
3 amino acids
Molecular weight
578.8 Da

Handling

Diluent
Glycol or ethanol wetting step, then water or serum base
Typical mix
10 or 50 mL
Vial sizes
50, 100, 200 mg
Lyophilised
Sealed, cool and dry; freezer for long-term.
Reconstituted
Refrigerated in a preserved base.

Mixing

Needs a solvent bridge because of the palmitoyl chain.

Side effects

  • rareIrritation

Combining it

  • redundantmatrixyl-3000 — This is one of the two peptides inside Matrixyl 3000.
  • redundantghk-cu-topical — Same tripeptide backbone; the meaningful difference is copper delivery.
  • synergyl-ascorbic-acid — Unlike GHK-Cu this has no copper to be reduced, so it layers cleanly with vitamin C.

What to monitor

  • · Standardised photography at 0, 8 and 16 weeks.

Legal status

Cosmetic ingredient (INCI Palmitoyl Tripeptide-1) approved worldwide.

References

  • Sederma Biopeptide CL technical dossier (other)
  • Pickart & Margolina 2018, GHK-Cu review (background on the GHK backbone) (review)

Mechanism in depth

The important thing to understand about this compound is what the palmitoylation costs as well as what it buys. It buys penetration. It costs copper. GHK's copper-binding site is formed by the N-terminal amine, the first peptide nitrogen and the histidine imidazole — three nitrogens in a square-planar arrangement around Cu(II). Acylating the N-terminal amine with palmitic acid removes one of those three coordinating nitrogens, which is precisely why palmitoyl tripeptide-1 is not blue and does not deliver copper. So everything in the GHK-Cu literature that depends on copper — lysyl oxidase cofactor supply, SOD1 induction, the copper-responsive transcriptional programme, the antioxidant enzyme effects — does not transfer. What does transfer is the matrikine arm: collagen I and IV, fibronectin, hyaluronic acid and glycosaminoglycan output in fibroblasts. Then there is the interesting wrinkle. Once esterases cleave the palmitoyl chain in the dermis, you have free GHK with its copper site restored, sitting in a tissue that contains copper. So the compound may function as a prodrug that reconstitutes an active copper complex at the target rather than in the bottle — which would be a genuinely smart piece of design if anyone had demonstrated it. Nobody has. It is a mechanistic possibility, and I am flagging it as such rather than as a finding. Practically, this is the peptide inside Matrixyl 3000 and one of the four actives in Haloxyl, so most people using it are using it without knowing.

What usually goes wrong

The solubility trap catches most DIY formulators — palmitoylated peptides will not dissolve in plain water, and dumping powder into a water-based serum gives you a gritty suspension that separates. Wet it with pentylene glycol, propylene glycol or ethanol first. The second issue is assuming it is interchangeable with GHK-Cu. It is not; it is the copper-free, better-penetrating half of that molecule, and the parts of the GHK-Cu literature that people find most exciting are the copper-dependent parts. Third, evidence attribution: almost every human dataset involving this peptide comes from studying Matrixyl 3000 or Haloxyl, not the peptide alone.

Pharmacokinetics

Crosses blood-brain barrier
no
Metabolism
Skin esterases and amidases cleave the palmitoyl bond, releasing free GHK in the viable epidermis and dermis — which is the elegant part of the design, because the lipid is a delivery vehicle that is removed on arrival. The released GHK can then scavenge endogenous copper and partially reconstitute an active copper complex in situ.
Elimination
No meaningful systemic exposure. Palmitic acid released by cleavage enters normal lipid pools in trivial quantities.

Receptor targets

  • Unidentified fibroblast matrikine receptor — No receptor cloned, no Kd published

    Increased collagen I and IV, fibronectin, hyaluronic acid and glycosaminoglycan synthesis.

  • Copper(II) binding — only after esterase cleavage of the palmitoyl group — Free GHK binds Cu(II) with log K around 16; the intact palmitoylated form does not bind copper at all

    Hypothetical in-situ reconstitution of an active copper complex in the dermis. Unproven.

What to expect, and when

Week 8-12 for the first visible change, week 16-24 for a fair assessment. Identical to the rest of the matrikine family, because it is one.

Stacking and comparisons

The single practical advantage over GHK-Cu is that this layers cleanly with L-ascorbic acid, because there is no copper to be reduced and no Fenton chemistry to set off. If your routine is built around a morning vitamin C serum and you want GHK signalling anyway, this is the form to use. It also layers with acids and retinoids without complaint. The redundancy warnings matter more here than usual: palmitoyl tripeptide-1 is inside Matrixyl 3000 and inside Haloxyl, so a routine containing an eye cream with Haloxyl, a serum with Matrixyl 3000 and a standalone palmitoyl tripeptide-1 product is paying three times for one ingredient. Check INCI lists rather than product names.

Against GHK-Cu: better penetration, no copper, no blue stain, no vitamin C conflict, and none of the copper-dependent biology. Against Tripeptide-1 (free GHK): better penetration, but free GHK retains its copper-binding site and can pick up endogenous copper immediately rather than waiting for esterase cleavage. Against Matrixyl: same delivery strategy, different matrikine sequence, and Matrixyl has the randomised trial. If you want one lipopeptide matrikine with evidence, use pal-KTTKS; if you want the GHK backbone in a vitamin-C-compatible routine, use this.

Rough cost

$8–$50/month. Raw powder around $25-70 per gram used at 50-200 ppm, so effectively negligible per month for DIY. Finished products $12-50 a month. Market observation, not a sourced pricing study.

Genuinely uncertain

  • The in-situ copper reconstitution hypothesis — that esterase cleavage in the dermis restores an active GHK-Cu complex — is mechanistically plausible and completely undemonstrated.
  • No independent human trial of palmitoyl tripeptide-1 alone exists.
  • No permeation study has quantified how much better palmitoylation actually makes delivery for this specific peptide.
  • The molecular weight of 578.8 Da in the Core record is consistent with Pal-GHK but is unconfirmed against a primary source.
  • Whether the copper-free form retains any of the MMP/TIMP rebalancing that makes GHK-Cu interesting for photoaged skin is unknown.

Papers