NOVEL PEPTIDES, USE THEREOF IN COSMETIC AND COSMECEUTIC APPLICATIONS, AND COMPOSITIONS COMPRISING SAME
A peptide of formula I (SEQ ID NO: 1): Lip-A-Gly-His-B-R (I) wherein: Lip is a lipoyl residue of R or S configuration; A is absent or is a lysine residue of configuration L or D; GIy is a glycine residue; His is a histidine residue of configuration L or D; B is a lysine residue of configuration L or D, or a lysine residue of configuration L or D in which the NH2 group of the side chain comprises a modification, wherein said modification is (i) a replacement with a hydrogen or (ii) a modification with a protecting group selected from the group consisting of acetyl, benzoyl, tosyl, sulfonyl benzene, benzyloxycarbonyle and palmitoyl; wherein R is O(Z) or N(Z′)(Z′), and wherein Z, Z′ and Z′ are independently of each other a hydrogen or a protecting group selected from the group consisting of methyl, ethyl, propyl, phenyl, hexyl, decyl and hexadecyl, or a racemate, an enantiomer or a diastereomer thereof, or a mixture thereof, or a salt thereof. A peptide of formula II (SEQ ID NO: 2): Lip-A-His-B-C-Trp-R (II) wherein: Lip is a lipoyl residue of configuration R or S; His is a histidine residue of configuration L; Trp is a tryptophane residue of configuration L; A is absent, is an amino acid residue of configuration L or D selected from the group consisting of a lysine residue, an alanine residue, a glutamic acid residue and a glycine residue, or is a spacer of formula: NH—(CH2)n-CO— wherein n is an integer comprised between 2 and 14; B is an aromatic amino acid residue of configuration D selected from the group consisting of a phenylalanine residue, a homophenylalanine residue, a tryptophane residue, a β-(1-Naphthyl)-alanine residue, a β-(2-Naphthyl)-alanine residue and a phenylglycine residue; C is a basic amino acid residue of configuration L selected from the group consisting of an arginine residue, a lysine residue, an ornithine residue and a homoarginine residue; wherein R is O(Z) or N(Z′)(Z′),
1 . A peptide of formula I (SEQ ID NO: 1):
Lip-A-Gly-His-B-R (I)
wherein:
Lip is a lipoyl residue of R or S configuration;
A is absent or is a lysine residue of configuration L or D;
Gly is a glycine residue;
B is a lysine residue of configuration L or D, or a lysine residue of configuration L or D in which the NH 2 group of the side chain comprises a modification, wherein said modification is (i) a replacement with a hydrogen or (ii) a modification with a protecting group selected from the group consisting of acetyl, benzoyl, tosyl, sulfonyl benzene, benzyloxycarbonyle and palmitoyl;
His is a histidine residue of configuration L or D; and
R is OZ or N(Z′)(Z″), wherein Z, Z′ and Z″ are independently of each other a hydrogen or a protecting group selected from the group consisting of methyl, ethyl, propyl, phenyl, hexyl, decyl and hexadecyl,
or a racemate, an enantiomer or a diastereomer thereof, or a mixture thereof, or a salt thereof.
2 . The peptide of claim 1 , wherein A is a lysine residue.
3 . The peptide of claim 1 , wherein B is a lysine residue of configuration L or D.
4 . The peptide of claim 1 , wherein R is NH 2 .
5 . The peptide of claim 1 , wherein at least one of the lysine and histidine residues are in configuration L.
6 . The peptide of claim 1 , wherein the lysine and histidine residues are in configuration L.
7 . The peptide of claim 1 , wherein the lipoyl residue is in configuration R.
8 . The peptide of claim 1 , wherein the lipoyl residue is in configuration S.
9 . The peptide of claim 1 , wherein said peptide is Lip-Lys-Gly-His-Lys-NH 2 (SEQ ID NO: 3).
10 . The peptide of claim 1 , wherein said peptide is Lip-Lys-Gly-His-Lys (SEQ ID NO: 4).
11 . The peptide of claim 1 , wherein said peptide is Lip-Gly-His-Lys-NH 2 (SEQ ID NO: 5).
12 . The peptide of claim 1 , wherein said peptide is Lip-Gly-His-Lys (SEQ ID NO: 6).
13 . The peptide of claim 1 , wherein said peptide is Lip-Lys-Gly-His-Lys-N(CH 3 ) 2 (SEQ ID NO: 7).
14 . The peptide of claim 1 , wherein said peptide is Lip-Gly-His-Lys-N(CH 3 ) 2 (SEQ ID NO: 8).
15 . A peptide of formula II (SEQ ID NO: 2)
Lip-A-His-B-C-Trp-R (II)
wherein:
Lip is a lipoyl residue of configuration R or S;
His is a histidine residue of configuration L;
Trp is a tryptophane residue of configuration L;
A is absent, is an amino acid residue of configuration L or D selected from the group consisting of a lysine residue, an alanine residue, a glutamic acid residue and a glycine residue, or is a spacer of formula: NH—(CH 2 )n-CO— wherein n is an integer comprised between 2 and 14;
B is an aromatic amino acid residue of configuration D selected from the group consisting of a phenylalanine residue, a homophenylalanine residue, a tryptophane residue, a β-(1-Naphthyl)-alanine residue, a β-(2-Naphthyl)-alanine residue and a phenylglycine residue;
C is a basic amino acid residue of configuration L selected from the group consisting of an arginine residue, a lysine residue, an ornithine residue and a homoarginine residue; and
R is OZ or N(Z′)(Z″),
wherein Z, Z′ and Z″ are independently of each other a hydrogen or a protecting group selected from the group consisting of methyl, ethyl, propyl, phenyl, hexyl, decyl and hexadecyl,
or a racemate, an enantiomer or a diastereomer thereof, or a mixture thereof, or a salt thereof.
16 . The peptide of claim 15 , wherein the lipoyl residue is in configuration R.
17 . The peptide of claim 15 , wherein the lipoyl residue is in configuration S.
18 . The peptide of claim 15 , wherein A is absent.
19 . The peptide of claim 15 , wherein B is a phenylalanine residue.
20 . The peptide of claim 15 , wherein C is an arginine or an ornithine residue.
21 . The peptide of claim 15 , wherein C is an arginine residue.
22 . The peptide of claim 15 , wherein R is NH 2 .
23 . The peptide of claim 15 , wherein said peptide is Lip-His-DPhe-Arg-Trp-NH 2 (SEQ ID NO: 9).
24 . The peptide of claim 15 , wherein said peptide is Lip-Lys-His-DPhe-Arg-Trp-NH 2 (SEQ ID NO: 10).
25 . The peptide of claim 15 , wherein said peptide is Lip-His-Trp-Arg-Trp-NH 2 (SEQ ID NO: 11).
26 . The peptide of claim 15 , wherein said peptide is Lip-Lys-His-Trp-Arg-Trp-NH 2 (SEQ ID NO: 12).
27 . The peptide of claim 15 , wherein said peptide is Lip-His-DPhe-Orn-Trp-NH 2 (SEQ ID NO: 13).
28 . A composition comprising an effective amount of the peptide of claim 1 , and a topically, cosmetically or pharmaceutically acceptable excipient or carrier.
29 . The composition of claim 28 , wherein said effective amount is between about 10 −8 M to about 10 −2 M.
30 . The composition of claim 28 , wherein said effective amount is between about 10 −6 M to about 10 −5 M.
31 . The composition of claim 28 , wherein said composition is a topical composition.
32 . The composition of claim 31 , wherein said composition is an aqueous solution, a cream, a water-in-oil emulsion, a oil-in-water emulsion, a gel, a spray, an ointment, a lotion, or a paste.
33 . The composition of claim 28 , further comprising at least one additional active agent.
34 . The composition of claim 33 , wherein said at least one additional active agent is a UV filter.
35 . The composition of claim 33 , wherein said at least one additional active agent is another peptide of Formula I or II.
36 - 57 . (canceled)
58 . A method of:
(i) preventing, reducing, delaying or treating a skin condition in a biological system; or
(ii) photo protecting a biological system against UVA- and/or UVB-induced damages; or
(iii) inhibiting IL-1α-induced IL-8 production in a biological system; or
(iv) increasing glutathione regeneration in a biological system; or
(v) increasing glutathione scavenging activity in a biological system; or
(vi) preventing, reducing, delaying or treating free radicals-induced inflammation in a biological system; or
(vii) any combination of (i) to (vi),
said method comprising administering an effective amount of the peptide of claim 1 , to said biological system.
59 . The method of claim 58 , wherein said method is for preventing, reducing, delaying or treating a skin condition in a biological system, and said skin condition is an aging-related skin condition.
60 . The method of claim 59 , wherein said aging-related skin condition is the appearance or presence of (a) wrinkles, (b) fine lines or (c) both (a) and (b), on the skin.
61 . The method of claim 58 , wherein said method is for preventing, reducing, delaying or treating a skin condition in a biological system, and said skin condition is a skin injury.
62 . The method of claim 61 , wherein said skin injury is associated with surgical treatment, dermabrasion, laser treatment or peeling.
63 . The method of claim 58 , wherein said method is for preventing, reducing, delaying or treating a skin condition in a biological system, and said skin condition is a photo aging-related skin condition.
64 . (canceled)
65 . The method of claim 64 , wherein said method is for photo protecting a biological system against UVA- and/or UVB-induced damages, and the damages include UV-induced DNA modifications.
66 . The method of claim 64 , wherein said method is for photo protecting a biological system against UVA- and/or UVB-induced damages, and the damages include UV-induced oxidative lesions.
67 - 70 . (canceled)
71 . The method of claim 58 , wherein said biological system is a cell, a tissue or an organ.
72 . The method of claim 71 , wherein said cell is a skin cell.
73 . The method of claim 71 , wherein said organ is skin.
74 . A kit or package comprising the peptide of claim 1 , together with instructions for preventing, reducing, delaying or treating a skin condition in a subject.
75 . The kit or package of claim 74 , further comprising a UV filter.
76 . A kit or package comprising the peptide of claim 1 , and a container.
77 - 78 . (canceled)