Dermatopontin-activating peptides and cosmetic compositions including same

1. A peptide of general formula (I):

R 1 -(AA) n -X 1 -Arg-X 2 -Trp-X 3 -X 4 -X 5 -X 6 (R 3 )-(AA) p -R 2

wherein,

X 1 is aspartic acid or absent,

X 2 is glutamine or glutamic acid,

X 3 is asparagine or lysine or glutamine or absent,

X 4 is phenylalanine or tyrosine or absent,

X 5 is tyrosine or alanine or absent,

X 6 is cysteine or absent,

AA is any amino acid and n and p are integers between 0 and 2,

R 1 is the primary amine function of the N-terminal amino acid, free or substituted by a group of the acyl type (R—CO—) wherein the radical R is either a saturated or unsaturated C 1 to C 30 alkyl chain of the acetyl type, or an aromatic group of the benzoyl, tosyl, or benzyloxycarbonyl type,

R 2 is the hydroxyl group of the carboxyl function of the C-terminal amino acid, substituted by a group chosen from a C 1 to C 10 alkyl chain, or an NH 2 , NHY or NYY group with Y representing a C 1 to C 4 alkyl chain or one of the salts thereof,

R 3 is the thiol function of cysteine in the X 6 position, wherein the thiol function is free or substituted by a methyl group or an acetyl group, or the thiol function is covalently bound by a disulfide bond to another cysteine;

with the proviso that when X 1 is absent, n is 0.

2. The peptide of claim 1 , wherein said peptide of general formula (I) is

(SEQ ID NO: 1)

Asp-Arg-Gln-Trp-NH 2 ,

(SEQ ID NO: 2)

Asp-Arg-Glu-Trp-NH 2 ,

(SEQ ID NO: 3)

Asp-Arg-Gln-Trp-Asn-Tyr-NH 2 ,

(SEQ ID NO: 4)

Arg-Glu-Trp-Gln-Phe-Tyr-Cys-NH 2 ,

(SEQ ID NO: 5)

Arg-Glu-Trp-Gln-Phe-Tyr-Cys(Cys)-(NH 2 ),

(SEQ ID NO: 6)

Asp-Arg-Glu-Trp-Gln-Phe-NH 2 ,

(SEQ ID NO: 7)

Asp-Arg-Gln-Trp-Asn-Tyr-Ala-Cys-NH 2 ,

(SEQ ID NO: 8)

Asp-Arg-Gln-Trp-Asn-Tyr-Ala-Cys(Cys)-(NH 2 ),

(SEQ ID NO: 9)

Asp-Arg-Glu-Trp-Gln-Phe-Tyr-Cys-NH 2 ,

(SEQ ID NO: 10)

Asp-Arg-Glu-Trp-Gln-Phe-Tyr-Cys(Cys)-(NH 2 ),

(SEQ ID NO: 11)

Asp-Arg-Gln-Trp-Lys-Phe-NH 2 ,

(SEQ ID NO: 12)

Arg-Glu-Trp-Gln-Phe-Tyr-NH 2 .

3. The peptide of claim 1 , wherein said peptide of general formula (I) is solubilized in one or more physiologically acceptable solvents selected from the group consisting of water, glycerol, ethanol, propanediol, butylene glycol, dipropylene glycol, the ethoxylated or propoxylated diglycols, the cyclic polyols, and mixtures of these solvents.

4. A cosmetic composition comprising:

a peptide of general formula (I):

R 1 -(AA) n -X 1 -Arg-X 2 -Trp-X 3 -X 4 -X 5 -X 6 (R 3 )-(AA) p -R 2

wherein,

X 1 is aspartic acid or absent,

X 2 is glutamine or glutamic acid,

X 3 is asparagine or lysine or glutamine or absent,

X 4 is phenylalanine or tyrosine or absent,

X 5 is tyrosine or alanine or absent,

X 6 is cysteine or absent,

AA is any amino acid and n and p are integers between 0 and 2,

R 1 is the primary amine function of the N-terminal amino acid, free or substituted by a group of the acyl type (R—CO—) wherein the radical R is either a saturated or unsaturated C 1 to C 30 alkyl chain of the acetyl type, or an aromatic group of the benzoyl, tosyl, or benzyloxycarbonyl type,

R 2 is the hydroxyl group of the carboxyl function of the C-terminal amino acid, substituted by a group chosen from a C 1 to C 30 alkyl chain, or an NH 2 , NHY or NYY group with Y representing a C 1 to C 4 alkyl chain or one of the salts thereof,

R 3 is the thiol function of cysteine in the X 6 position, wherein the thiol function is free or substituted by a methyl group or an acetyl group, or the thiol function is covalently bound by a disulfide bond to another cysteine; and

a physiologically acceptable medium,

wherein said peptide of formula (I) is a dermatopontin-activating agent; and

with the proviso that when X 1 is absent, n is 0.

5. The composition of claim 4 , wherein said peptide is present in a concentration of between 10 −9 M and 10 −3 M with respect to the total weight of the composition.

6. The composition of claim 4 wherein the composition is suitable for topical administration.

7. The composition of claim 4 further comprising at least one other active agent.

8. The composition of claim 4 , wherein said peptide is present in a concentration of between 10 −8 M and 10 −5 M with respect to the total weight of the composition.

9. The composition of claim 4 , wherein said peptide of general formula (I) is

(SEQ ID NO: 1)

Asp-Arg-Gln-Trp-NH 2 ,

(SEQ ID NO: 2)

Asp-Arg-Glu-Trp-NH 2 ,

(SEQ ID NO: 3)

Asp-Arg-Gln-Trp-Asn-Tyr-NH 2 ,

(SEQ ID NO: 4)

Arg-Glu-Trp-Gln-Phe-Tyr-Cys-NH 2 ,

(SEQ ID NO: 5)

Arg-Glu-Trp-Gln-Phe-Tyr-Cys(Cys)-(NH 2 ),

(SEQ ID NO: 6)

Asp-Arg-Glu-Trp-Gln-Phe-NH 2 ,

(SEQ ID NO: 7)

Asp-Arg-Gln-Trp-Asn-Tyr-Ala-Cys-NH 2 ,

(SEQ ID NO: 8)

Asp-Arg-Gln-Trp-Asn-Tyr-Ala-Cys(Cys)-(NH 2 ),

(SEQ ID NO: 9)

Asp-Arg-Glu-Trp-Gln-Phe-Tyr-Cys-NH 2 ,

(SEQ ID NO: 10)

Asp-Arg-Glu-Trp-Gln-Phe-Tyr-Cys(Cys)-(NH 2 ),

(SEQ ID NO: 11)

Asp-Arg-Gln-Trp-Lys-Phe-NH 2 ,

(SEQ ID NO: 12)

Arg-Glu-Trp-Gln-Phe-Tyr-NH 2 .

10. The composition of claim 4 , wherein said peptide of general formula (I) is solubilized in one or more physiologically acceptable solvents selected from the group consisting of water, glycerol, ethanol, propanediol, butylene glycol, dipropylene glycol, the ethoxylated or propoxylated diglycols, the cyclic polyols, and mixtures of these solvents.

11. A method of treating the cutaneous signs of aging and photoaging, the method comprising:

providing a composition comprising a peptide of general formula (I):

R 1 -(AA) n -X 1 -Arg-X 2 -Trp-X 3 -X 4 -X 5 -X 6 (R 3 )-(AA) p -R 2

wherein,

X 1 is aspartic acid or absent,

X 2 is glutamine or glutamic acid,

X 3 is asparagine or lysine or glutamine or absent,

X 4 is phenylalanine or tyrosine or absent,

X 5 is tyrosine or alanine or absent,

X 6 is cysteine or absent,

AA is any amino acid and n and p are integers between 0 and 2,

R 1 is the primary amine function of the N-terminal amino acid, free or substituted by a group of the acyl type (R—CO—) wherein the radical R is either a saturated or unsaturated C 1 to C 30 alkyl chain of the acetyl type, or an aromatic group of the benzoyl, tosyl, or benzyloxycarbonyl type,

R 2 is the hydroxyl group of the carboxyl function of the C-terminal amino acid, substituted by a group chosen from a C 1 to C 30 alkyl chain, or an NH 2 , NHY or NYY group with Y representing a C 1 to C 4 alkyl chain or one of the salts thereof,

R 3 is the thiol function of cysteine in the X 6 position, wherein the thiol function is free or substituted by a methyl group or an acetyl group, or the thiol function is covalently bound by a disulfide bond to another cysteine; and

applying the composition to the skin before or after exposure to the sun;

with the proviso that when X 1 is absent, n is 0.

12. The method of claim 11 , wherein the peptide is an active agent that increases the expression of proteins of the extracellular matrix by the fibroblasts of the skin or increases regeneration of the epidermis and dermis.

13. The method of claim 11 , wherein applying occurs after exposure to sun, and the composition reduces degradation of collagen and elastic fibers in the skin.

14. The method of claim 11 , wherein said peptide is present in a concentration of between 10 −9 M and 10 −3 M with respect to the total weight of the composition.

15. The method of claim 11 , wherein said peptide of general formula (I) is

(SEQ ID NO: 1)

Asp-Arg-Gln-Trp-NH 2 ,

(SEQ ID NO: 2)

Asp-Arg-Glu-Trp-NH 2 ,

(SEQ ID NO: 3)

Asp-Arg-Gln-Trp-Asn-Tyr-NH 2 ,

(SEQ ID NO: 4)

Arg-Glu-Trp-Gln-Phe-Tyr-Cys-NH 2 ,

(SEQ ID NO: 5)

Arg-Glu-Trp-Gln-Phe-Tyr-Cys(Cys)-(NH 2 ),

(SEQ ID NO: 6)

Asp-Arg-Glu-Trp-Gln-Phe-NH 2 ,

(SEQ ID NO: 7)

Asp-Arg-Gln-Trp-Asn-Tyr-Ala-Cys-NH 2 ,

(SEQ ID NO: 8)

Asp-Arg-Gln-Trp-Asn-Tyr-Ala-Cys(Cys)-(NH 2 ),

(SEQ ID NO: 9)

Asp-Arg-Glu-Trp-Gln-Phe-Tyr-Cys-NH 2 ,

(SEQ ID NO: 10)

Asp-Arg-Glu-Trp-Gln-Phe-Tyr-Cys(Cys)-(NH 2 ),

(SEQ ID NO: 11)

Asp-Arg-Gln-Trp-Lys-Phe-NH 2 ,

(SEQ ID NO: 12)

Arg-Glu-Trp-Gln-Phe-Tyr-NH 2 .

16. The method of claim 11 , wherein said peptide of general formula (I) is solubilized in one or more physiologically acceptable solvents selected from the group consisting of water, glycerol, ethanol, propanediol, butylene glycol, dipropylene glycol, the ethoxylated or propoxylated diglycols, the cyclic polyols, and mixtures of these solvents.