Pentapeptide-18
C29H39N5O7
Research Use Only. Pentapeptide-18 is a research compound intended strictly for laboratory and scientific research purposes. It is not approved for human consumption, therapeutic use, or veterinary use. Information on this page is provided for educational and research reference purposes only.
Overview
Pentapeptide-18, also known by the trade name Leuphasyl and by its chemical designation [D-Ala2]leucine-enkephalin, is a synthetic five-amino-acid peptide that is structurally derived from enkephalins, which are naturally occurring neuropeptides found in the human nervous system. It belongs to a class of peptides sometimes referred to as neuropeptide-mimetic or neurotransmitter-inhibiting peptides, meaning it is designed to mimic certain signaling molecules involved in muscle activity at the cellular level. With a molecular weight of approximately 569.6 Da and the formula C29H39N5O7, it is a relatively compact and well-characterized compound that has attracted interest in laboratory settings. Researchers have investigated Pentapeptide-18 in the context of skin biology, particularly in studies examining the extracellular matrix and factors related to skin structure, often in combination with delivery systems such as lipid nanoparticles. All research involving Pentapeptide-18 is conducted strictly for scientific study purposes, and it is not approved or intended for human use or therapeutic application.
Compound Data
| CAS Number |
64963-01-5 |
| Molecular Formula |
C29H39N5O7 |
| Molecular Weight |
569.60 g/mol |
| IUPAC Name |
(2S)-2-[[(2S)-2-[[2-[[(2R)-2-[[(2S)-2-amino-3-(4-hydroxyphenyl)propanoyl]amino]propanoyl]amino]acetyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoic acid |
| PubChem CID |
10099522
|
Research & Bioactivity
Pentapeptide-18 is a synthetic enkephalin-like peptide that researchers have studied primarily in the context of skin biology, with particular interest in its potential effects on dermal extracellular matrix dynamics and facial muscle activity. Studies have examined its spectroscopic properties and molecular interaction profiles as part of efforts to characterize how peptides of this class may influence the structural components of skin, including collagen and elastin pathways associated with the aging process. Research has also investigated pentapeptide-18 as a component in lipid nanocarrier delivery systems, including solid lipid nanoparticles, where it has been combined with retinol to evaluate formulation stability, skin penetration, and compatibility as a cosmetic research material in both anti-aging and anti-acne study contexts. In vitro studies using human melanocyte models have explored modified analogs of pentapeptide-18 — specifically versions incorporating D-tyrosine at the terminal position — to investigate potential effects on tyrosinase activity and melanin synthesis, suggesting the peptide scaffold may serve as a platform for studying pigmentation-related biology. Collectively, the published research on pentapeptide-18 has been conducted primarily through in vitro cellular models, biophysical characterization methods, and formulation science approaches, rather than clinical human studies.
Also Known As
- 64963-01-5
- Leuphasyl
- [D-Ala2]leucine-enkephalin
- Pentapeptide-18
- (D-Ala2)leucine-enkephalin
- PO4D55T1IG
- NSC-374895
- RefChem:1094532
- 265-291-0
- Tyr-D-Ala-Gly-Phe-Leu
- H-Tyr-D-Ala-Gly-Phe-Leu-OH
- (D-Ala2)-Leu-Enkephalin
- L-Leucine, L-tyrosyl-D-alanylglycyl-L-phenylalanyl-
- MFCD00076409
- [D-Ala2]-Leu-Enkephalin
Published Research
Pentapeptide-18 as an anti-aging candidate: Spectroscopic characterization and molecular interaction analysis.
Akhan D, Bicak B, Akalin E, Gunduz SK — 2026
Skin aging is predominantly associated with the progressive breakdown of the dermal extracellular matrix (ECM), leading to visible manifestations such as wrinkle development caused by repetitive facial muscle movements and a gradual reduction in collagen and elastin synthesis. This degeneration is intensified by external factors including ultraviolet exposure, tobacco use, and nutritional imbalance, which interfere with major intracellular signaling pathways-namely TGF-β, TNF-α, MAPK, PI3K/AKT, and NF-κB-that collectively regulate inflammatory responses, oxidative stress, and ECM remodeling. Pentapeptide-18 (Leuphasyl®), a bioactive peptide known for its neuromodulatory properties, has demonstrated the ability to mitigate wrinkle formation by inhibiting neurotransmitter release, while simultaneously improving skin hydration, elasticity, and texture. In this study, the anti-aging activity of Pentapeptide-18 was comprehensively examined through a combination of experimental analyses and computational modeling. Structural optimization and electronic property evaluation were performed using density functional theory (DFT) calculations with the 6-31 + +G(d,p) basis set, complemented by frontier molecular orbital (HOMO-LUMO) and molecular electrostatic potential (MEP) analyses. Theoretical vibrational frequencies were assigned via potential energy distribution (PED) analysis and validated experimentally using FTIR, ATR-FTIR, and Raman spectroscopy. Additionally, molecular docking and molecular dynamics simulations were employed to investigate the binding behavior of Pentapeptide-18 with key molecular targets implicated in skin aging, including TGF-β, TNF-α, MAPK, PI3K/AKT, and NF-κB. Pharmacokinetic and drug-likeness properties were further assessed through ADMET (absorption, distribution, metabolism, excretion, and toxicity). The collective findings provide mechanistic insight into the molecular interactions and stability of Pentapeptide-18, reinforcing its potential as a safe, effective, and non-invasive candidate for advanced anti-aging skin care applications.
Retinol and Oligopeptide-Loaded Lipid Nanocarriers as Effective Raw Material in Anti-Acne and Anti-Aging Therapies.
Pawłowska M, Marzec M, Jankowiak W, Nowak I — 2024
The use of lipid nanocarriers as components of cosmetic formulations may provide an opportunity to fully exploit the beneficial properties of pentapeptide-18 and retinol while reducing the undesirable effects that occur during retinoid therapy. This study aimed to evaluate the effectiveness of semi-solid formulations enriched with retinol and oligopeptide-loaded lipid nanocarriers. Solid lipid nanoparticles were produced using a high-shear homogenization method. The work included physicochemical characterization of the cosmetic products, and evaluation of their stability as well as their efficacy. The resulting semi-solid preparations were determined to be stable regardless of their storage temperature. No effect of the presence of lipid nanoparticles on the shelf-life stability of the cosmetic products was observed. A temperature of 25 °C was considered the recommended storage temperature for the tested semi-solid formulations. Beneficial effects of the cosmetic products were proven (in vivo study on volunteers), i.e., a significant reduction in the level of sebum secretion (anti-acne therapy) and a decrease in the number of facial wrinkles (anti-aging therapy). In addition, the protective properties of the lipid nanoparticles themselves against the skin were confirmed, reducing the irritating effect of retinol that is usually the case with classic retinoid therapies.
Solid Lipid Nanoparticles Incorporated with Retinol and Pentapeptide-18-Optimization, Characterization, and Cosmetic Application.
Pawłowska M, Marzec M, Jankowiak W, Nowak I — 2024
Solid lipid nanoparticles (SLNs) incorporated with retinol and oligopeptide can have a full spectrum of effects on the skin as a compatible combination of ingredients with broad anti-aging properties. The research's main objective was to ensure the stability of lipid nanocarriers containing retinol and peptide due to the planned use of this dispersion as a cosmetic raw material. To confirm the effectiveness of method optimization (high shear homogenization, HSH) and proper selection of substrates, SLN dispersions were obtained in three combinations: 1-non-incorporated SLNs; 2-SLNs containing only retinol; 3-SLNs containing retinol and pentapeptide-18; these were then stored at different temperatures (4, 25, 45 °C) for 4 weeks. The desired values of the physicochemical parameters of the optimized dispersion of lipid nanoparticles incorporated with retinol and oligopeptide over the required storage period were confirmed: mean particle size (Z-Ave) = 134.7 ± 0.3 nm; polydispersity index (PDI) = 0.269 ± 0.017 [-]; zeta potential (ZP) = 42.7 ± 1.2 mV (after 4 weeks at 25 °C). The results confirmed the proper selection of the SLN production method and the effectiveness of the optimization performed. The possibility of using the obtained raw material as an ingredient in cosmetic products with anti-aging properties was indicated.
D-tyrosine adds an anti-melanogenic effect to cosmetic peptides.
Park J, Jung H, Jang B, Song HK, Han IO, et al. — 2020
D-tyrosine is known to negatively regulate melanin synthesis by inhibiting tyrosinase activity. Here, we further reveal that peptides containing terminal D-tyrosine can reduce the melanin contents of human melanocytes. The addition of D-tyrosine to the terminus of the commercial anti-wrinkle peptide, pentapeptide-18 endowed the peptide with the ability to reduce the melanin content and tyrosinase activity in human MNT-1 melanoma cells and primary melanocytes. Consistently, terminal D-tyrosine-containing pentapeptide-18 inhibited the melanogenesis induced by α-MSH treatment or UV irradiation of MNT-1 cells and reduced melanin synthesis in the epidermal basal layer of a 3D human skin model. Furthermore, the addition of D-tyrosine to an anti-aging peptide (GEKG) or an anti-inflammatory peptide (GHK) endowed these short peptides with anti-melanogenic effects without altering their intrinsic effects. Together, these data suggest that the addition of D-tyrosine at the terminus of a short cosmetic peptide adds an anti-melanogenic effect to its intrinsic cosmetic effect. Our work offers a novel means of generating dual-function cosmetic peptides.