Most peptides in our organism, released by cells or cleaved from proteins, circulating in the blood or acting on nearby structures, are essentially effective as signaling molecules, i.e. hormones (ορμ´ο ν η = messenger). They interact with a specific receptor molecule on the outside of a cell (or at the nucleus within the cell) due to mutual recognition of complementary chemistry and 3D structure. In other cases, the peptide is recognized by an enzyme which it then inhibits or stimulates. In all cases, it is the quite precise arrangement of the chemical structure of the peptide (its sequence and 3D conformation) that will govern the interaction—and its intensity and efficacy—with the recognizing cell, protein or other structure. We have mentioned that the simple switch of Lysine and Histidine in the sequences of GHK and GKH leads to widely differing yields in synthesis; even more to the point is the fact that GHK (as a copper chelate15 or a palmitoyl derivative16 possesses collagen stimulating activity, whereas the GKH peptide (especially its palmitoylated species) has lipolytic activity on adipocytes.
Although most peptides that are on the cosmetic market are based on some "story" on a biological justification for their choice and on a connection to well-documented processes in the skin physiology, investigation into the precise mechanisms of action is often lacking: do the peptides act on keratinocytes? Do they bind to specific receptors on the cell membrane? Do they enter keratinocytes? Do they penetrate all the way to fibroblasts? And do they interact with surface receptors, or do they act on the nuclei? Even the various DNA array studies, although demonstrating high specificity for these peptides do not tell us all that happens when the peptide is applied topically. Indirect cascade events, cell-to-cell communication across the various layers of the skin may contribute as much to the observed activities as direct peptide/receptor binding.
The question of delivery and skin penetration needs to be addressed. Small, charged peptides have very little chance of making it through the stratum corneum. Adding a lipophilic fatty acid chain, a biomimetic idea, increases the diffusion rate of the peptide into the skin, all the while keeping it within this tissue. Other tricks of delivery enhancement have been described in numerous papers. Be it liposomal inclusion, dermaporation, fusion with TAT sequences, iontophoresis and its sibling PowerPaper® technology (patches with a self-contained battery included, able to deliver charged molecules from a gel-imbibed tissue to the skin via electric current), they all attempt to help the peptides cross the stratum corneum barrier. True clinical benefits of these delivery and release technologies have yet to be demonstrated in sufficiently large panels, comparing an "optimized" peptide formulation with a "standard" formulation, the difficulty being that for each peptide sequence this optimum may be different. Nor is it clear what becomes of the peptide once applied to the skin: proteolytic enzymes abound in the epidermis, even the stratum corneum contains trypsine, chymotrypsine and similar proteins which may shorten the life span of a susceptible peptide dramatically. It is well known that in the blood stream, peptide hormones (angiotensin, bradykinine, vasopressine and many others of similar type) have half lives of a few minutes; their signaling/triggering job being designed to last only a short while, the downstream cascade having much longer effects. It is somewhat comparable to switching on a light bulb: the time and energy needed to push the button is in no relation to the duration of the bulb and the energy released over time. That is how peptides, even in cosmetic, topical applications, can be so potent at such low (ppm) concentrations.
This information is an excerpt from the book Chemistry and Manufacture of Cosmetics: Cosmetic Specialties and Ingredients. To learn more about this topic or to purchase the entire book, visit www.AlluredBooks.com.
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