Peptides have recently generated interest as biologically active compounds incorporated into cosmeceutical products intended to treat aging skin. Peptides are composed of chains of amino acids, which are derived from DNA transcription. In typical cellular settings, peptides communicate or signal between DNA and the cellular network. Consequently, they are thought to be capable of being used or exploited to direct cells to maintain youthful behavior, yielding a stable, nonaging manifestation. In addition, peptides can be rendered by protein degradation, thus forming an essential feedback inhibition and upregulation loop (Facial Plast. Surg. 2009;25:285-9). Downregulation of metalloproteinases (MMPs), notably collagenase, by peptides is a good example, as well as a window into why peptides have sparked interest within antiaging research (Dermatol. Surg. 2005;31[7 Pt 2]:832-6, discussion 836).
Researchers at the University of Tennessee, Memphis, performed some of the seminal work that has paved the way for understanding how to harness the activity of natural peptides by showing that the production of the extracellular matrix in fibroblasts is fostered by a pentapeptide subfragment of propeptide of type I collagen (J. Biol. Chem. 1993;268:9941-4).
But the foundational work setting the stage for development of cosmeceutical peptides has been in the research for ameliorating wounds, which dates back several decades and can be traced to the use of yeast extracts for wound care in the 1930s, later leading to the extraction of a usable protein fraction (Dermatol. Ther. 2007;20:343-9; Clin. Ther. 1991;13:430-4). Signal peptides, enzyme-inhibitor peptides, neurotransmitter-inhibitor peptides (or neuropeptides), and carrier peptides are the four primary classes of topical or cosmeceutical peptides. This column will offer a brief summary of each and acknowledge additional recent research. Future columns may address each of these peptide categories pertinent to antiaging cosmeceuticals.
Signal peptides
Specific bioactive amino acid chains have been discovered in recent years that promote human skin dermal fibroblast growth in vitro and in vivo, and reduce the length and depth of wrinkles (Dermatol. Ther. 2007;20:343-9). The most popular signal peptide is the lysine-threonine-threonine-lysine-serine (KTTKS) located on type 1 procollagen. To enhance epidermal delivery, it has been linked to palmitic acid, thus the marketed version (Matrixyl) is a palmitoyl pentapeptide, which has been shown to augment the synthesis of collagen by fibroblasts and yield reductions in fine lines and wrinkles, according to quantitative analysis and self-reports (J. Biol. Chem. 1993;268:9941-4; Int. J. Cosmet. Sci. 2005;27:155-60).
New signal peptides are expected to be stronger and better targeted than those presently marketed (Facial Plast. Surg. 2009;25:285-9). Signal peptides promote the synthesis of matrix proteins, collagen in particular, which leads to firmer, younger looking skin, and also augments levels of elastin, proteoglycans, glycosaminoglycans, and fibronectin (Int. J. Cosmet. Sci. 2009;31:327-45).
Enzyme-inhibitor peptides
These peptides suppress enzymatic activity either directly or indirectly. Enzyme-inhibiting peptides extracted from soybeans have been incorporated into antiaging, moisturizing, and cleansing products as well as hair care formulations (Int. J. Cosmet. Sci. 2009;31:327-45). In a small study in 10 white females, a 2% soya biopeptide performed better than did placebo in collagen and glycosaminoglycan promotion (Int. J. Cosmet. Sci. 1999;21:299-311).
More recently, a rice peptide derived from germinated black rice, which has been used in traditional Asian medicines, was found to block MMP activity and dose-dependently stimulate hyaluronan synthase 2 gene expression (a twofold increase) in human keratinocytes (J. Microbiol. Biotechnol. 2007;17:271-9). Such peptides are found in antiaging and hair products.
In addition, antioxidant activity, a high affinity to chelate with copper, and the capacity to suppress tyrosinase activity and keratinocyte apoptosis have been displayed by the enzyme-inhibiting peptide sericin, derived from the silkworm Bombyx mori (Int. J. Cosmet. Sci. 2009;31:327-45). Sericin also has been shown to facilitate the intrinsic moisturization of skin by restoring amino acids and imparting an occlusive effect (J. Cosmet. Dermatol. 2005;4:250-7).
Neuropeptides
Neuropeptides are known to mediate skin inflammation and, thus, contribute as an underlying aspect of reactive skin conditions (Eur. J. Dermatol. 2010;20:731-7). Also known as neurotransmitter-affecting peptides, these compounds are included in cosmeceuticals to mimic the action of botulinum toxin A. Essentially, they inhibit acetylcholine release at the neuromuscular junction.
The best known of these is acetyl hexapeptide-3, marketed as Argireline. Attached to acetic acid residue, this synthetic peptide, based on the N-terminal end of the synaptosomal-associated protein (SNAP)–25 that blocks soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) complex development and catecholamine release (Int. J. Cosmet. Sci. 2009;31:327-45), is thought to suppress the release of neurotransmitters, easing facial tension, and thus reducing wrinkles. Evidence of its effectiveness has appeared largely in proprietary studies. Much more research is necessary to establish the suitability of this form of peptide for topical antiaging applications.