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Article

New peptides aspire to induce chemical change, but data can be questionable

In addition to efforts on the collagen front is another movement to develop peptides to mimic the activities of botulinium toxin in the neuro-muscular junction.

NEWEST REALM

Many moisturizers currently on the market use a hydrocolloid protein that forms a large molecular-weight film over the surface of the skin to retard the evaporation of water with an artificial barrier and get rid of the fine lines.

"This is the newest realm in cosmeceuticals and we can expect many, many more products to come," says Dr. Draelos, a clinical associate professor at Wake Forest University in Winston-Salem, N.C., and an editorial adviser to Dermatology Times.

University of Tennessee researchers led the charge to design collagen-modulating peptides by exposing a specific pentapeptide to a subconfluent fibroblast culture, and concluding that the combination upregulated the production of collagen 1. Procter & Gamble subsequently obtained an exclusive licensing contract for the peptide, called matrixyl, and it is patented by Sederma in France.

But unlike hydracollic moisturizers, the new, engineered peptides cannot simply function on the surface of the skin.

"In order to reprogram collagen, they need to get to the dermis and penetrate the stratum corneum," Dr. Draelos explains.

Free fatty acids were identified as an ideal way to accomplish that by driving the peptide into the skin without damaging the stratum corneum or causing too much irritant contact dermatitis. The scientists specifically linked one free fatty acid, palmitic acid, to deliver their pentapeptide into the skin, and they found that when the pentapeptide was placed in a Petri dish culture, there was a synthesis of collagen 1, collagen 3 and fibronectin.

The product is chemically referred to as Pal-KTTKS and versions of similar peptides linked to palmitic acid carriers that have been developed include Syn-Coll, distributed by Centerchm, Matrixyl 3000 and others.

"All of these have some type of biologic activity, but the question is how much and how often," Dr. Draelos says.

MECHANISM OF ACTION

The theory on how the peptides work is that the skin responds to the flood of breakdown products of collagen by downregulating collagenase, which upregulates collagen 1 production. But Dr. Draelos questions that suggestion.

"While it may make sense, unfortunately the skin doesn't work like that," she explains. "The fact is, collagen production is not an equilibrium reaction."

On the horizon for newer collagen modulating peptides is Sepilift DPHP, a plant-derived amino acid that is marketed by SEPPIC (see related story, p. s25). The peptide, due to make its debut in a number of new products entering the marketplace in 2006, inhibits the synthesis of matalloproteinases and is being marketed for its estradiol-like activities.

PEPTIDES' ROLE

In addition to efforts on the collagen front is another movement to develop peptides to mimic the activities of botulinium toxin in the neuromuscular junction. The movement began with gaba-based neurotransmitters, but those products quickly exited the market due largely to their inactivity.

In their place is a hexapeptide fragment also developed by Sederma. Commercially known as Argireline, the peptide is usually found in concentrations of 3 percent to 10 percent and is said to modulate the formation of the SNARE complex, a key characteristic of botulinium toxin.

But the activity on the SNARE complex between the toxin and the peptides are not the same, Dr. Draelos says.

"Whereas botulinium toxin breaks the SNARE complex, these products theoretically destabilize it. Their market is moisturizers, and these peptides may indeed be hydrocolloids, and not neuromuscular junction peptides, as advertised."

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