Helix Biomedix Inc.

Lijuan Zhang

Timothy John Falla

Scott M Harris

Robin Carmichael

Timothy J Falla

Timothy Falla

Scott Harris

Short biologically active tetrapeptides are disclosed that are comprised of the sequences GxxG and PxxP where G (glycine) and P (proline) are maintained and x is a variable amino acid. The peptides can be used singly or in combination to stimulate production of extracellular matrix proteins in skin. A rapid, low-cost method of producing heterogenous formulations of tetrapeptides is disclosed.

Peptide fragments for inducing synthesis of extracellular matrix proteins

Tetrapeptides consisting of (I or V)-X1-K-X2, where X1 can be selected from E, Q or K, and X2 can be selected from M, F, I, W, or V, exhibit diverse bioactivities. They are multi-functional effector molecules to stimulate keratinocytes migration; neutralize the proinflammatory effect of bacterial cell wall components such as lipoteichoic acids of the Gram-positive; and induce angiogenesis in cultured human umbilical vein endothelial cells. The downregulation of pro-inflammatory condition was also demonstrated using SOR-300-FT psoriasis skin model for representative peptide. The bioactivity was also supported by gene profiling study upon treatment of normal skin tissues using EPIDERM&#x2122; skin substitutes. The inventive peptides with diverse bioactivities are useful for treating various skin conditions including, but not limited to, acute or chronic wounds, striae distensae, aging skin, hair control, inflammatory skins such as psoriasis, atopic dermatitis and rosacea and for unwanted hair removal or for conditions such as removal of skin tags.

Tetrapeptides derived from human C-X-C chemokines useful for treatment of various skin conditions

The invention relates to small molecules having biological and therapeutic activity. Particularly, the invention relates to small molecules having lipolytic and anti-adipogenic activity. Two examples of such molecules are 4-methyl-2-(octanoylamino) pentanoic acid and N-isopentyloctanamide. The invention further relates to methods of preventing or treating skin conditions such as cellulite using small molecules having lipolytic and anti-adipogenic activity.

N-acyl amino acid derivatives for treating skin conditions such as cellulite

Peptides having four to six amino acid residues are disclosed that possess biological activity. These peptides constitute short fragments of the peptide HB-107 (MPKEKVFLKIEKMGRNIRN) (SEQ ID NO: 10), which itself is a fragment of the antimicrobial protein cecropin B, and exhibit cell stimulatory and migratory properties. The inventive peptides comprise four to six contiguous amino acid residues located between position 11 and 16 of HB107 (MPKEKVFLKIEKMGRNIRN) (SEQ ID NO: 10), namely EKMGRN (SEQ ID NO: 1). The disclosed peptides comprise a useful agent for the medical treatment of injury to the skin, such as from diabetic ulcers. The peptides also are effective in preventing and reversing skin surface damage resulting from various environmental insults. Importantly, the therapeutic effects of the peptides manifest at concentrations equal to or greater than those of peptide HB-107 (SEQ ID NO: 10), and thus represent a less expensive, more versatile means for developing effective therapies. Methods for the production and use of these peptides are also disclosed.

Short bio-active peptides for promoting wound healing

Disclosed are peptides having biological and therapeutic activity. Particularly disclosed are lipidated di- or tri-peptides analogs of KPV or KdPT that exhibit antimicrobial activity. In particular, the peptides of this invention provide enhanced anti-microbial activity over the base tri-peptides, lysine-proline-valine and lysine-d-proline-tyrosine. The disclosed peptides have the general formula of C12-18 lipid-KXZ-NHi wherein K is lysine; X is proline, d-proline, histidine or arginine; Z is optional and if present Z is valine, threonine, alanine or leucine; and the terminal COOH is NHamidated. The C12-18 lipid is preferably the lipid moiety of lauric acid (C12), myristic acid (C14), pentadecanoic acid (C15), palmitic acid (C16), or stearic acid (C18). The invention is further related to methods of using of these peptides to treat various insults, inflammations or bacterial infections affecting the skin and other related mucosal body surfaces such as the oral cavity.

Short antimicrobial lipopeptides

Short peptides having biological and therapeutic activity are disclosed. Specifically, the activity of the disclosed peptides is directed to reducing or protecting against mutagen-induced cellular/tissue toxicity (i.e., chemopreventive). For example, the disclosed peptides protect against skin toxicity and/or mutagenesis that occurs from ultraviolet (UV) light exposure. The disclosed peptides also block the activation of certain cell cycle regulatory proteins such as Chk2. An example of such a peptide is Ser-Leu-Tyr-Gln-Ser (SEQ ID NO: 10). The disclosed peptides are also useful for methods of reducing or protecting against cellular toxicity and mutation accumulation that would otherwise occur following mutagen exposure. One such method is drawn to applying a peptide to the skin to prevent or reduce mutagenic damage resulting from UV light (e.g., sunlight) exposure.

Peptide protection against ultraviolet light toxicity

The disclosed invention provides tetrapeptides with the amino acid sequence proline-glutamine-glutamate-X (P-Q-E-X), where X can be either lysine (K) or isoleucine (I). These tetrapeptides inhibit ultraviolet light (UV)-induced expression of the pro-inflammatory cytokine interleukin-6 (IL-6) by skin epithelial cells and fibroblasts. Furthermore, the tetrapeptides repress the upregulation of matrix metalloproteinase-1 (MMP-1) by skin fibroblasts induced by either direct exposure to UV rays or treatment with media conditioned by UV-treated keratinocytes. The small size and bio-activity of the tetrapeptides render them suitable for use in therapies directed to inflammatory skin disorders and as active ingredients in skin care products.

Protective skin care peptides

Peptides having four to fourteen residues are disclosed that possess biological activity. These peptides constitute short fragments of the peptide HB-107 (SEQ ID NO:1), which itself is a fragment of the antimicrobial protein cecropin B, and exhibit cell stimulatory, migratory and anti-inflammatory properties. As keratinocytes are especially sensitive to these effects, the disclosed peptides comprise a useful agent for the medical treatment of injury to the skin, such as from diabetic ulcers. The peptides also are effective in preventing and reversing skin surface damage resulting from various environmental insults. Importantly, the therapeutic effects of the peptides manifest at concentrations equal to or greater than those of peptide HB-107, and thus represent a less expensive, more versatile means for developing effective therapies. Methods for the production and use of these peptides are also disclosed.

Short bio-active peptides for cellular and immunological modulation

The invention encompasses hexapeptides consisting of alternating hydrophobic residues (B) at positions 2, 4, and 6, hydrophilic, charged residues (X) at positions 1 and 3, and a naphthylalanine (Nal), an aliphatic or aromatic residue (O) at position five, represented generally by the formula XBXBOB, which exhibit antimicrobial activity against infections caused by a variety of pathogens. These pathogens may include gram positive or negative bacteria, acid-fast bacteria such as mycobacteria, parasites, dermatophytes, or fungal pathogens. Typical fungal pathogens includeand typical dermatophytes includeand. The hexapeptides of the present invention exhibit antifungal activity, antibacterial activity, desirable stability, and lack toxicity to the mammal receiving treatment.

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Kenmore, WA, United States of America

Lijuan Zhang