Laurie Verzeaux, Hélène Muchico, Elodie Aymard and Brigitte Closs, Silab04.21.23
Today, more than ever, cosmetic brands must prove the safety and the efficacy of their products. Even though the cosmetic active ingredients market is constantly advancing, peptides nevertheless remain among the indispensable reference molecules. Indeed, they are commonly included in care products because of their potent efficacy and elevated safety.
Peptides are small chains of 2 to 50 amino acids linked by peptide bonds.1 As peptide chains form between joining of the primary structure of amino acids, they may enlarge to become oligopeptides, which gather between 10 to 20 amino acids in the chain. Beyond 20 amino acids, the peptide is an unbranched chain named a polypeptide (Figure 1).
Figure 1. Schematic representation of amino acids, peptides and protein organization.
They have been divided into four main groups, corresponding to their mechanism of action: i) signal peptides, which stimulate matrix protein production such as collagen or elastin, and cell metabolic functions like cell growth; ii) carrier peptides; iii) neurotransmitter-inhibitor peptides and iv) enzyme-inhibiting peptides.
Peptides are naturally-occurring biological molecules that can be synthesized by all the cells of the organisms. They ensure varied activities required for the correct functioning of the organism, depending on the nature and sequence of their component amino acids.2
The development of synthetic peptides for skin care dates back to the 1980s.3 Especially revered for their capacity to combat the first signs of aging, peptides have become veritable reference molecules in cosmetics. Anti-wrinkles, antioxidant, anti-inflammatory or healing, their mechanisms of action in many physiological processes make peptides attractive for many skin-related indications. Most of the peptides used in cosmetics are designed to counteract the skin aging process. According to Mintel, 50% of women in China associate oligopeptides with anti-aging benefits.4
Figure 2a & 2b. Schematic representation of the obtention of synthetic peptide (A) and natural peptides (B).
Natural peptides are obtained by the hydrolysis of proteins in small fragments, exposing peptides previously protected inside three-dimensional structures (Figure 2B). There are numerous sources to obtain natural peptides, from plants to microorganisms. Indeed, roots, stems, leaves, flowers, microalgae, yeasts and bacteria all contain proteins. The combination of resulting natural peptides is endless, when coupling these diverse raw materials to enzymes able to hydrolyze proteins. Enzyme choice is based on the nature of the raw material to hydrolyze and the enzyme properties. It is also possible to use combinations of enzymes to refine the selection of resulting peptides. The reaction must be stopped at the right time in order to avoid excessive cascade reactions that denature the desired product. This is done by an irreversible thermal inactivation of the enzyme that modifies its active site. The inactivated enzyme is now simply an inert reaction compound that no longer influences the final product. According to ISO 16128 concerning cosmetic products, the enzymatic hydrolysis reaction creates ingredients of natural origin. The resulting diversity of peptides derived from enzymatic hydrolysis enables one to achieve specific bio-activity thanks to this unique process.
“Microorganisms are genuine factories that can produce molecules with high added value,” said Sylvain Mazalrey, biotechnologies laboratory manager, Silab. “Beyond constitutive proteins, our expertise in biotechnologies enabled us to derive maximal benefit from the potential of these infinitely small microorganisms in order to orient the synthesis of peptides of interest.”
As a result of its know-how in enzyme engineering, Silab has constructed a toolbox that currently contains more than 40 perfectly-mastered enzymes. In addition to hydrolysis-based approaches, other green chemical processes such as biopolymerization were developed to assemble peptides and to enhance their efficacy, an approach currently applied primarily to the development of phytotensors.
Remaining faithful to its desire to innovate, Silab has continued to perfect its purification technologies to propose peptide concentrates that are increasingly more highly purified. In this context, the company recently strengthened its technological arsenal by investing in an industrial resin chromatography technology, in particular for selecting peptides based on their physiochemical properties, including ionicity and polarity.
From the diversification of raw materials used as sources of peptides to the optimization of its extraction and purification processes, many improvements have been implemented during the past 30 years to sustain and improve the “success story” of natural peptides. Resulting from the constant advances of its areas of expertise, the company is now in a position to propose about 20 active ingredients dedicated to face and body care, with multiple applications, such as anti-aging, barrier function recovery and complexion radiance. The elevated efficacies of their active peptide fractions have been scientifically proven.
Peptilium (INCI: Vaccinium Macrocarpon Fruit Extract) a natural anti-aging active ingredient with peptides purified to 95%. The elevated protein content of cranberries combined with the company’s eco-responsible values have made the press cake of this fruit a raw material of choice for optimizing the value of natural peptides. Enzyme engineering and purification expertise result in a peptide concentrate that combines richness and performance. The sequential action of two specifically-selected proteases has enabled the optimized extraction of all the peptides of interest present in this cranberry co-product. The use of molecular sorting combined with purification by ion exchange chromatography on resin enables the active fraction to subsequently be concentrated in natural peptides particularly rich in arginine (Figure 3).
Figure 3. Process adapted to the extraction of natural peptides from cranberry fruit press cakes.
The molecular diversity of Vaccinium Macrocarpon Fruit Extract provides overall anti-aging performance. The biological activity of this active ingredient has been determined in vitro by the use of a targeted transcriptomics study. About 30 genes governing homeostasis of the skin barrier and matrix restructuring have been studied. It was shown that 81% of these genes are regulated by Vaccinium Macrocarpon Fruit Extract. This effect in Caucasian and Asian volunteers is shown by a radiance booster anti-aging effect. The cosmetic benefits of this active ingredient are visible after 21 days of treatment, compared to 42 days for retinol. Vaccinium Macrocarpon Fruit Extract also has a positive effect on the barrier function but without the side effects associated with retinol, such as irritation and discomfort.
Lightskin (INCI: Yeast extract) is composed of natural depigmenting sulfur-containing peptides obtained by bioguiding. They are natural, depigmenting sulfur-containing peptides. At a time when perfection of the complexion and naturality are very important for many consumers, special attention was paid to sulfur-containing molecules with elevated depigmenting potential. In this context, the yeast Ogataea siamensis was selected for its unique metabolism and its ability to naturally synthesize sulfur-containing peptides. In order to benefit from this potential, the company relied on its biotechnology expertise to develop a specific bioguiding process. The strategy provides Ogataea siamensis with cysteine, an amino acid with an atom of sulfur and an indispensable precursor for the production of sulfur-containing molecules. The bioguided Ogataea siamensis culture was subjected to an enzymatic process. Under the action of a carbohydrase, the cell walls of the yeast were de-structured, an essential step for the extraction of the sulfur-containing fraction. The bioguiding process, coupled with enzymatic extraction, increases sulfur-containing peptides. It is a modification of molecular composition that doubles the depigmenting efficacy of the resulting active ingredient (Figure 4).
Figure 4. Process for bioguiding Ogataea siamensis for the production and extraction of depigmenting sulfur-containing peptides.
This bioguiding process applied specifically to the yeast Ogataea siamensis has thus made it possible to obtain a complex mixture of odorless sulfur-containing peptides that provides transversal depigmenting efficacy in the contexts of glycation and pollution. Tested on human melanocytes from Caucasian and Asian subjects, the resulting active ingredient significantly limits the activity of tyrosinase and the synthesis of melanin. This activity is shown in vivo by improving pigment defects. The active ingredient enriched in sulfur-containing peptides was evaluated in volunteers selected on the basis of several criteria, including the presence of spots on the face and also high levels of AGEs (in Caucasian volunteers) or a history of living in a polluted urban environment (in Asian volunteers). It significantly reduces the appearance of spots in these volunteers and improves uniformity of the complexion. These effects are confirmed by Caucasian volunteers, more than 80% of whom report their skin to be more uniform and luminous. More than 90% of Asian volunteers judged their spots to be less visible.
References
Peptides are small chains of 2 to 50 amino acids linked by peptide bonds.1 As peptide chains form between joining of the primary structure of amino acids, they may enlarge to become oligopeptides, which gather between 10 to 20 amino acids in the chain. Beyond 20 amino acids, the peptide is an unbranched chain named a polypeptide (Figure 1).
Figure 1. Schematic representation of amino acids, peptides and protein organization.
Peptides are naturally-occurring biological molecules that can be synthesized by all the cells of the organisms. They ensure varied activities required for the correct functioning of the organism, depending on the nature and sequence of their component amino acids.2
The development of synthetic peptides for skin care dates back to the 1980s.3 Especially revered for their capacity to combat the first signs of aging, peptides have become veritable reference molecules in cosmetics. Anti-wrinkles, antioxidant, anti-inflammatory or healing, their mechanisms of action in many physiological processes make peptides attractive for many skin-related indications. Most of the peptides used in cosmetics are designed to counteract the skin aging process. According to Mintel, 50% of women in China associate oligopeptides with anti-aging benefits.4
Natural or Synthetic?
Most peptides on the cosmetics market are synthetics.3 Indeed, peptide synthesis is a technology commonly used to produce peptides of interest with a defined sequence. Peptides are chemically synthesized by the condensation reaction of the carboxyl group of one amino acid to the amino group of another (Figure 2A). While they stand out due to their elevated biological specificity, these peptides obtained by chemical processes have only limited activity toward a unique biological target. Moreover, if chemical synthesis displays precise tailor-made synthesis, they can have bad environmental credentials. At the present time, this lack of transversality and of naturality is no longer consistent with the needs and expectations of consumers who are demanding natural, multifunctional and effective products.5Figure 2a & 2b. Schematic representation of the obtention of synthetic peptide (A) and natural peptides (B).
Obtaining Natural Peptides
Since its founding, Silab has focused on optimizing the value of natural peptides for cosmetic uses. Initially, the company used raw materials of animal origin. In the 1990s, adjusting to regulatory restrictions imposed on the cosmetics industry, Silab expanded its sources of peptides, by exiting the animal kingdom and focusing on the universe of plants and microorganisms. The company extracts natural peptides by developing eco-extraction processes specific to each raw material. Sources of raw material are numerous: fruits, plants, cereals, co-products and by-products. Biotechnology is also a tremendous source of peptides.“Microorganisms are genuine factories that can produce molecules with high added value,” said Sylvain Mazalrey, biotechnologies laboratory manager, Silab. “Beyond constitutive proteins, our expertise in biotechnologies enabled us to derive maximal benefit from the potential of these infinitely small microorganisms in order to orient the synthesis of peptides of interest.”
As a result of its know-how in enzyme engineering, Silab has constructed a toolbox that currently contains more than 40 perfectly-mastered enzymes. In addition to hydrolysis-based approaches, other green chemical processes such as biopolymerization were developed to assemble peptides and to enhance their efficacy, an approach currently applied primarily to the development of phytotensors.
Remaining faithful to its desire to innovate, Silab has continued to perfect its purification technologies to propose peptide concentrates that are increasingly more highly purified. In this context, the company recently strengthened its technological arsenal by investing in an industrial resin chromatography technology, in particular for selecting peptides based on their physiochemical properties, including ionicity and polarity.
From the diversification of raw materials used as sources of peptides to the optimization of its extraction and purification processes, many improvements have been implemented during the past 30 years to sustain and improve the “success story” of natural peptides. Resulting from the constant advances of its areas of expertise, the company is now in a position to propose about 20 active ingredients dedicated to face and body care, with multiple applications, such as anti-aging, barrier function recovery and complexion radiance. The elevated efficacies of their active peptide fractions have been scientifically proven.
New Product Development
Silab’s newest peptides are derived from plants and yeast. Here are details on several of them.Peptilium (INCI: Vaccinium Macrocarpon Fruit Extract) a natural anti-aging active ingredient with peptides purified to 95%. The elevated protein content of cranberries combined with the company’s eco-responsible values have made the press cake of this fruit a raw material of choice for optimizing the value of natural peptides. Enzyme engineering and purification expertise result in a peptide concentrate that combines richness and performance. The sequential action of two specifically-selected proteases has enabled the optimized extraction of all the peptides of interest present in this cranberry co-product. The use of molecular sorting combined with purification by ion exchange chromatography on resin enables the active fraction to subsequently be concentrated in natural peptides particularly rich in arginine (Figure 3).
Figure 3. Process adapted to the extraction of natural peptides from cranberry fruit press cakes.
Lightskin (INCI: Yeast extract) is composed of natural depigmenting sulfur-containing peptides obtained by bioguiding. They are natural, depigmenting sulfur-containing peptides. At a time when perfection of the complexion and naturality are very important for many consumers, special attention was paid to sulfur-containing molecules with elevated depigmenting potential. In this context, the yeast Ogataea siamensis was selected for its unique metabolism and its ability to naturally synthesize sulfur-containing peptides. In order to benefit from this potential, the company relied on its biotechnology expertise to develop a specific bioguiding process. The strategy provides Ogataea siamensis with cysteine, an amino acid with an atom of sulfur and an indispensable precursor for the production of sulfur-containing molecules. The bioguided Ogataea siamensis culture was subjected to an enzymatic process. Under the action of a carbohydrase, the cell walls of the yeast were de-structured, an essential step for the extraction of the sulfur-containing fraction. The bioguiding process, coupled with enzymatic extraction, increases sulfur-containing peptides. It is a modification of molecular composition that doubles the depigmenting efficacy of the resulting active ingredient (Figure 4).
Figure 4. Process for bioguiding Ogataea siamensis for the production and extraction of depigmenting sulfur-containing peptides.
Conclusion
Peptides are essential molecules in cosmetics. The growing demand from consumers for naturality and transparency makes natural peptides molecules of great interest. Consistent with its philosophy of innovation, Silab has used its adaptability and know-how to optimize the value of natural peptides by the continuous development of new extraction and purification technologies. Natural peptides, one of the cornerstones of the company’s success for decades, remain at the heart of strategic developments.References
- Forbes, Jessica, et Karthik Krishnamurthy. « Biochemistry, Peptide ». StatPearls, StatPearls Publishing, 2022.
- Zhang, L. & Falla, T. J. Cosmeceuticals and peptides. Clin Dermatol 27, 485–494 (2009).
- Ferreira, M. S., Magalhães, M. C., Sousa-Lobo, J. M. & Almeida, I. F. Trending Anti-Aging Peptides. Cosmetics 7, 91 (2020).
- KuRunData/Mintel, March 2022
- Mintel Portal | Connexion. https://portal.mintel.com/portal/login?next=https%3A%2F%2Fclients.mintel.com%2Freport%2Fa-year-of-innovation-in-facial-skincare-2022
