INTRODUCTION
The extracellular matrix (ECM) is the foundational platform of the skin, incorporating the fibroblast cellular protein factory in a structural matrix of proteins that provide support to the dermis and epidermis, as well as the superficial vascular complex. It also provides important signaling cues to the constituents of both the dermis and epidermis that greatly impact cellular proliferation and vital skin functions.1
Peptides have been used very successfully to impact fibroblast and epithelial cells, optimize cellular functionality, and improve cross-talk between cells and proteins, altering gene expression and creating translational protein production that assists in regeneration.6,7 To that end, an exploration was undertaken on the amino acid sequences and spacing of collagen and elastin to try to elucidate a pattern that could produce a peptide that would mimic the functionality of these important structural proteins. This paper elucidates the scientific thought processes, validation steps, and successful incorporation of a novel peptide into skin formulations.
The dynamic reciprocity and cross-talk that takes place between the proteins and cells provides an ongoing conversation that ensures constant recycling of the ECM with robust signaling between these entities.2,3 Intrinsic aging and extrinsic photodamage result in an alteration within the ECM, wherein an accumulation of degraded waste products tends to "clog up" the ECM and interfere with this cross-talk. This results in inefficient signaling and replacement of the ECM, creating aging manifestations and impedance of healing processes and scarring potential.4,5
Peptides have been used very successfully to impact fibroblast and epithelial cells, optimize cellular functionality, and improve cross-talk between cells and proteins, altering gene expression and creating translational protein production that assists in regeneration.6,7 To that end, an exploration was undertaken on the amino acid sequences and spacing of collagen and elastin to try to elucidate a pattern that could produce a peptide that would mimic the functionality of these important structural proteins. This paper elucidates the scientific thought processes, validation steps, and successful incorporation of a novel peptide into skin formulations.
In the Beginning . . .
So many interesting facts can be mined when digging deeper into the most important structural proteins in the skin:
- There are 19 total amino acids in collagen (tryptophan contributes negligibly): alanine, arginine, asparagine, aspartate, cysteine, glutamate, glutamine, glycine, histidine, isoleucine, leucine, lysine, methionine, phenylalanine, proline, serine, threonine, tyrosine, and valine. Collagen is missing the essential amino acid, tryptophan. Fifty percent of the 19 amino acids in collagen are heavily concentrated in glycine and proline8 (Figure 1).
- The triple helical structure of the alpha chain of collagen has a repeating common sequence, with glycine appearing as every third residue -- Gly -X-Y- Gly . . . and the X and Y being any amino acid but most commonly including proline.8 Glycine is the smallest amino acid, and its presence as every third residue imparts stability to the helical structure.8 Thus, it would make logical sense to try to include glycine in the new sequence and to repeat it in a third sequence where possible. Additionally, proline as the extra amino acid with this sequence would also appear to make sense from a structural stability perspective (Figure 1).
