3AA Limited Human
Syn-Coll (Palmitoyl Tripeptide-5)
A palmitic acid-capped Lys-Val-Lys tripeptide that hijacks the thrombospondin-1 signalling axis to flood fibroblasts with TGF-β, driving a dual surge in collagen synthesis and a shutdown of the MMP-1/MMP-3 enzymes that degrade it.
In Plain English:
Syn-Coll is the trade name for Palmitoyl Tripeptide-5, a synthetic cosmetic active developed by Pentapharm (Switzerland, founded 1948) and now owned by dsm-firmenich following its 2007 acquisition. The molecule is three amino acids — lysine, valine, lysine (Lys-Val-Lys) — attached to a 16-carbon palmitic acid tail. The tail is not decorative: it dramatically improves penetration through the stratum corneum by making the otherwise hydrophilic peptide lipid-compatible, boosting skin residence time and enabling it to reach live dermal fibroblasts. Once there, the Lys-Val-Lys sequence mimics the active domain of thrombospondin-1 (TSP-1), a naturally occurring extracellular matrix glycoprotein. TSP-1 is the body's principal activator of latent TGF-β, and Syn-Coll piggybacks on that pathway: it triggers TGF-β release, which then drives fibroblasts to upregulate collagen type I and type III mRNA transcription. Simultaneously, Syn-Coll inhibits the matrix metalloproteinases MMP-1 and MMP-3 that degrade newly synthesised collagen and suppress pro-inflammatory cytokines that cause capillary permeability and vasodilation. The net result is a build-and-protect action on the extracellular matrix. In a 84-day manufacturer study (n=45), twice-daily application at 1% and 2.5% reduced wrinkle appearance by 7% and 12% respectively. A separate 84-day open-label clinical study (Trookman et al., 2009, n=37) using a multi-ingredient formulation anchored by Palmitoyl Tripeptide-5 showed statistically significant improvement in periocular and perioral fine and coarse wrinkle scores at every timepoint — within minutes, at Month 1, and at Month 3 — with 86% of subjects reporting softening of fine lines and no treatment-related adverse events. In vitro, the peptide at 3 ppm stimulated Type I collagen synthesis by 119% versus untreated controls, and supplier data report roughly 60% greater collagen-building efficacy than Palmitoyl Pentapeptide (Pal-KTTKS). An independent 2025 review (Badilli & Inal, Polymers) confirms the TSP-1 mimicry mechanism. The ingredient is registered under INCI as Palmitoyl Tripeptide-5 (formerly Palmitoyl Tripeptide-3 before a 2010 INCI revision). CAS 623172-56-5 covers the TFA salt used in research; CAS 623172-55-4 covers the free-base cosmetic form. Two-year shelf life when stored at 2–8 °C. No reported sensitisation, toxicity, or endocrine disruption in published literature or CIR review. EWG Skin Deep rates it low hazard across all concern categories.
Research Maturity
Limited Human (~8 relevant papers; no standalone RCT — 1 multi-ingredient open-label trial, rest manufacturer/in vitro+ Studies)
Focus
Collagen Support
Skin & Aesthetics
Origin
Developed by Pentapharm AG, Basel, Switzerland — a pharmaceutical peptide synthesis firm founded in 1948 that pivoted to cosmeceuticals. Syn-Coll launched in the early 2000s as a patented lipo-tripeptide. The Lys-Val-Lys sequence was selected because it mirrors a functional motif in thrombospondin-1 responsible for activating latent TGF-β in the extracellular matrix. Royal DSM acquired Pentapharm in July 2007; following the 2023 merger with Firmenich, the product line sits under dsm-firmenich Beauty & Care as SYN®-COLL CB. The product is manufactured under Green Chemistry principles, is 99% natural-origin by ISO 16128, readily biodegradable per OECD 301, and produced with 100% renewable electricity. Carbon footprint certified at 5.2 kg CO₂ eq./kg. The INCI name was previously Palmitoyl Tripeptide-3; the revision to Palmitoyl Tripeptide-5 was made in the 2010 INCI cycle — the molecule is identical. CIR assessed the palmitoyl oligopeptide class (2012 safety review) and found the family safe for cosmetic use at marketed concentrations.
Mechanism
Palmitoyl Tripeptide-5 operates through a thrombospondin-1 (TSP-1) mimicry mechanism. TSP-1 is a multifunctional extracellular matrix glycoprotein that activates latent TGF-β by disrupting its inhibitory latency-associated peptide (LAP) complex; the active domain responsible is a short sequence that the Lys-Val-Lys tripeptide replicates. On reaching dermal fibroblasts, Syn-Coll engages the same receptor pathway — confirmed by Murphy-Ullrich & Poczatek (2000, Cytokine Growth Factor Rev., doi: 10.1016/s1359-6101(99)00029-5) — releasing active TGF-β1. Active TGF-β1 binds its cell-surface receptors (TGF-βRI/II) and initiates SMAD2/3 phosphorylation. SMAD2/3 translocate to the nucleus as a complex with SMAD4 and drive transcription of extracellular matrix genes, in particular those encoding collagen type I α1 (COL1A1), collagen type III α1 (COL3A1), and fibronectin (FN1), producing a persistent increase in steady-state mRNA levels (Varga et al., 1987, Biochem J., doi: 10.1042/bj2470597). On the protective side, Syn-Coll suppresses MMP-1 (interstitial collagenase, degrades type I collagen) and MMP-3 (stromelysin-1, degrades type III collagen, fibronectin, laminin, proteoglycans, elastin), reducing enzymatic collagen breakdown (Errante et al., 2020, Front. Chem., doi: 10.3389/fchem.2020.572923). Additionally, it downregulates pro-inflammatory cytokine production, limiting cytokine-driven vasodilation and capillary permeability. The C16 palmitoyl tail increases log P, facilitating passive diffusion across the lipid-rich stratum corneum and extending epidermal residence time. The combined dual mechanism — simultaneous collagen synthesis stimulation and collagen degradation inhibition — differentiates Syn-Coll from matrikine-class peptides that operate solely via matrix fragment signalling.
Outcome
Manufacturer 84-day study (n=45 volunteers, twice-daily topical, 1% and 2.5% Palmitoyl Tripeptide-5): wrinkle appearance reduced by 7% at 1% concentration and 12% at 2.5%; PRIMOS surface topography measurements showed approximately 3.5-fold improvement versus placebo in wrinkle depth reduction. Manufacturer 4-week study (n=33 female Chinese volunteers): 77% reported visible improvement in skin firmness and elasticity; 60% reported reduction in pore appearance. Trookman NS et al. (2009, J Clin Aesthetic Dermatol, PMCID PMC2923951): open-label, single-centre, 37 female subjects aged 33–45, 3-month twice-daily application of a multi-ingredient formulation anchored by Palmitoyl Tripeptide-5. Periocular fine wrinkle score improved significantly at all timepoints (P<0.0001 vs baseline from within minutes through Month 3); perioral fine wrinkle improvements reached P≤0.0003 at all timepoints. Subject self-assessment at Month 3: 86% reported softening of fine lines around eyes, 83% reported smoother skin appearance, 80% reported brightened eye area. Erythema score decreased from 0.78 to 0.57; no treatment-related adverse events. Relatable Science 2025 review cites a 12-week study (n=60 adults) reporting 15–30% reduction in wrinkle depth; a split-face study (8 weeks) found 21.6% reduction in nasolabial fold depth and 10% decrease in under-eye bags using Syn-Coll in nanoparticle/lactoferrin combination. Badilli & Inal (2025, Polymers, doi: 10.3390/polym17060798) cite a supramolecular nanoparticle formulation (Chen et al., 2025) achieving 10.22% reduction in under-eye bags and 21.57% reduction in nasolabial folds. In vitro (fibroblast culture): 3 ppm Palmitoyl Tripeptide-5 stimulated Type I collagen synthesis by 119% versus untreated controls; reported ~60% greater collagen stimulation than Palmitoyl Pentapeptide (Pal-KTTKS) under equivalent conditions. DSM-firmenich supplier data report 13–26% boost in collagen reserves depending on age group and concentration, and 2.5× UV-induced collagen protection. Note: the Trookman 2009 study used a multi-ingredient formulation; no standalone Palmitoyl Tripeptide-5 placebo-controlled RCT has been published independently of the manufacturer.
