Caffeoyl sh-Heptapeptide-13 è un heptapeptide sintetico arricchito con un derivato del caffè, l'acido caffeico, noto per le sue proprietà antiossidanti e protettive della pelle.

Synthetic peptides can be generated as copies of protein fragments by incorporating non-proteinogenic amino acids and modified so as to also increase the proteolytic stability of the molecules. Peptides are used in the development of therapeutic drugs (1) because of their antimicrobial activity (2), their bioactive interest (3).

The name describes the structure of the molecule:

• Caffeoyl is the presence of a caffeoyl group in the compound. Caffeoyl typically refers to a group derived from caffeic acid, a type of phenolic acid found in various plants, a caffeic acid-bound part of the compound attached to the peptide.
• sh stands for "signal human" "signal peptide," indicating that the peptide is designed to mimic natural human peptides or is synthesized for specific signaling functions in cosmetic or therapeutic applications.
• Heptapeptide indicates that the molecule consists of 7 amino acids linked together in a chain.
• 13 typically denotes a specific sequence or variant of heptapeptide, its unique identification or specific change in its sequence compared to other similar peptides.

What it is used for and where

Caffeoyl sh-Heptapeptide-13 is inserted in cosmetic formulations for its ability to protect the skin from free radical damage and harmful environmental factors. Acting as a powerful antioxidant, this peptide helps fight oxidation and prevent premature aging of the skin. Additionally, it strengthens the skin barrier, enhancing the skin's resistance against external aggressions and promoting healthier, more resilient skin. It is ideal for use in creams, serums, and protective treatments, particularly effective for those living in urban environments or exposed to pollutants.

Cosmetics - INCI Functions

• Antioxidant agent. Ingredient that counteracts oxidative stress and prevents cell damage. Free radicals, pathological inflammatory processes, reactive nitrogen species and reactive oxygen species are responsible for the ageing process and many diseases caused by oxidation.
• Skin protectant. It creates a protective barrier on the skin to defend it from harmful substances, irritants, allergens, pathogens that can cause various inflammatory conditions. These products can also improve the natural skin barrier and in most cases more than one is needed to achieve an effective result.

Industrial Production Process

• Reagent selection. High-quality reagents, including the ten amino acids making up the decapeptide and caffeic acid, are selected to ensure optimal efficacy and reactivity.
• Solid-phase peptide synthesis (SPPS). Using SPPS, the ten amino acids are sequentially assembled starting from the C-terminal amino acid, which is attached to a solid resin.
• Caffeoyl group coupling. After synthesizing the decapeptide, the caffeoyl group is chemically coupled to the N-terminus of the decapeptide. This step is crucial for imparting the peptide with its antioxidant and protective properties.
• Cleavage and deprotection. The complete peptide is released from the resin, and protective groups are removed using an appropriate cleavage mixture.
• Purification. The crude peptide is purified via reverse-phase chromatography to remove impurities and optimize product purity.
• Quality control. The purified product undergoes rigorous testing, including HPLC and mass spectrometry, to verify its purity, structure, and functionality.
• Formulation. Finally, the product is formulated with compatible ingredients in cosmetic products to maximize its effects on the skin.

References_____________________________________________________________________

(1) Myšková A, Sýkora D, Kuneš J, Maletínská L. Lipidization as a tool toward peptide therapeutics. Drug Deliv. 2023 Dec;30(1):2284685. doi: 10.1080/10717544.2023.2284685. 

Abstract. Peptides, as potential therapeutics continue to gain importance in the search for active substances for the treatment of numerous human diseases, some of which are, to this day, incurable. As potential therapeutic drugs, peptides have many favorable chemical and pharmacological properties, starting with their great diversity, through their high affinity for binding to all sort of natural receptors, and ending with the various pathways of their breakdown, which produces nothing but amino acids that are nontoxic to the body. Despite these and other advantages, however, they also have their pitfalls. One of these disadvantages is the very low stability of natural peptides. They have a short half-life and tend to be cleared from the organism very quickly. Their instability in the gastrointestinal tract, makes it impossible to administer peptidic drugs orally. To achieve the best pharmacologic effect, it is desirable to look for ways of modifying peptides that enable the use of these substances as pharmaceuticals. There are many ways to modify peptides. Herein we summarize the approaches that are currently in use, including lipidization, PEGylation, glycosylation and others, focusing on lipidization. We describe how individual types of lipidization are achieved and describe their advantages and drawbacks. Peptide modifications are performed with the goal of reaching a longer half-life, reducing immunogenicity and improving bioavailability. In the case of neuropeptides, lipidization aids their activity in the central nervous system after the peripheral administration. At the end of our review, we summarize all lipidized peptide-based drugs that are currently on the market.

(2) Nguyen HLT, Trujillo-Paez JV, Umehara Y, Yue H, Peng G, Kiatsurayanon C, Chieosilapatham P, Song P, Okumura K, Ogawa H, Ikeda S, Niyonsaba F. Role of Antimicrobial Peptides in Skin Barrier Repair in Individuals with Atopic Dermatitis. Int J Mol Sci. 2020 Oct 14;21(20):7607. doi: 10.3390/ijms21207607.

Abstract. Atopic dermatitis (AD) is a common chronic inflammatory skin disease that exhibits a complex interplay of skin barrier disruption and immune dysregulation. Patients with AD are susceptible to cutaneous infections that may progress to complications, including staphylococcal septicemia. Although most studies have focused on filaggrin mutations, the physical barrier and antimicrobial barrier also play critical roles in the pathogenesis of AD. Within the physical barrier, the stratum corneum and tight junctions play the most important roles. The tight junction barrier is involved in the pathogenesis of AD, as structural and functional defects in tight junctions not only disrupt the physical barrier but also contribute to immunological impairments. Furthermore, antimicrobial peptides, such as LL-37, human b-defensins, and S100A7, improve tight junction barrier function. Recent studies elucidating the pathogenesis of AD have led to the development of barrier repair therapy for skin barrier defects in patients with this disease. This review analyzes the association between skin barrier disruption in patients with AD and antimicrobial peptides to determine the effect of these peptides on skin barrier repair and to consider employing antimicrobial peptides in barrier repair strategies as an additional approach for AD management.

(3) Stephanopoulos N. Peptide-Oligonucleotide Hybrid Molecules for Bioactive Nanomaterials. Bioconjug Chem. 2019 Jul 17;30(7):1915-1922. doi: 10.1021/acs.bioconjchem.9b00259. Epub 2019 May 28. PMID: 31082220.

Abstract. Peptides and oligonucleotides are two of the most interesting molecular platforms for making bioactive materials. Peptides provide bioactivity that can mimic that of proteins, whereas oligonucleotides like DNA can be used as scaffolds to immobilize other molecules with nanoscale precision. In this Topical Review, we discuss covalent conjugates of peptides and DNA for creating bioactive materials that can interface with cells. In particular, we focus on two areas. The first is multivalent presentation of peptides on a DNA scaffold, both linear assemblies and more complex nanostructures. The second is the reversible tuning of the extracellular environment-like ligand presentation, stiffness, and hierarchical morphology-in peptide-DNA biomaterials. These examples highlight the potential for creating highly potent materials with benefits not possible with either molecule alone, and we outline a number of future directions and applications for peptide-DNA conjugates.