Peptides that stimulate subcutaneous adipogenesis
Peptides of 5 to 14 amino acids in length that stimulate subcutaneous adipogenesis and uses thereof are provided.
1. A pharmaceutical or cosmetic composition comprising a pharmaceutically or cosmetically acceptable carrier and a modified peptide or peptidomimetic, wherein the modified peptide or peptidomimetic is at least 6 amino acids in length, but not more than 8 amino acids in length, and comprises a motif having the sequence: KSEVSK (SEQ ID NO: 3), wherein the modified peptide:
comprises a protecting group, wherein the modified peptide has improved ex vivo and/or in vivo peptide stability and/or improved skin penetration when administered topically, relative to an unmodified peptide of the same sequence; or
is functionalized with a polymer selected from the group consisting of a polyethylene glycol, a cellulose, and a modified cellulose, wherein the modified peptide has increased bioavailability, relative to an unmodified peptide of the same sequence; and
wherein the peptidomimetic comprises one or more peptide linkages replaced with a linkage selected from the group consisting of —CH 2 NH—, —CH 2 S—, —CH 2 —CH 2 —, —CH═CH—, —COCH 2 —, —CH(OH)CH 2 —, and —CH 2 SO, wherein the peptidomimetic has an improvement in a property, relative to an unmodified peptide of the same sequence, wherein the property is selected from the group consisting of: economy of production, chemical stability, half-life, absorption, potency, efficacy, and/or reduced antigenicity.
2. The composition of claim 1 , wherein the modified peptide or peptidomimetic is 6 amino acids in length.
3. The composition of claim 1 , wherein the composition is for topical, subcutaneous, or transdermal administration.
4. The composition of claim 1 , wherein the composition is for injection.
5. The composition of claim 1 , wherein the composition further comprises collagen.
6. The composition of claim 5 , wherein the collagen is a bovine collagen, a porcine collagen, or a human collagen.
7. The composition of claim 5 , wherein the collagen is a synthetic collagen.
8. The composition of claim 1 , wherein the composition further comprises an anesthetic.
9. The composition of claim 8 , wherein the anesthetic comprises lidocaine.
10. The composition of claim 1 , wherein the composition is a skin cream.
11. The composition of claim 1 , wherein the modified peptide or peptidomimetic is a modified peptide comprising a protecting group, wherein the modified peptide has improved ex vivo and/or in vivo peptide stability and/or improved skin penetration when administered topically, relative to an unmodified peptide of the same sequence.
12. The composition of claim 11 , wherein the protecting group comprises an acetyl group at the amino-terminus of the modified peptide or peptidomimetic.
13. The composition of claim 1 , wherein the modified peptide or peptidomimetic is a modified peptide functionalized with a polymer selected from the group consisting of a polyethylene glycol, a cellulose, and a modified cellulose, wherein the modified peptide has increased bioavailability, relative to an unmodified peptide of the same sequence.
14. The composition of claim 1 , wherein the modified peptide or peptidomimetic is a peptidomimetic comprising one or more peptide linkages replaced with a linkage selected from the group consisting of —CH 2 NH—, —CH 2 S—, —CH 2 —CH 2 —, —CH═CH—, —COCH 2 —, —CH(OH)CH 2 —, and —CH 2 SO, wherein the peptidomimetic has an improvement in a property, relative to an unmodified peptide of the same sequence, wherein the property is selected from the group consisting of: economy of production, chemical stability, half-life, absorption, potency, efficacy, and/or reduced antigenicity.
15. A modified peptide or peptidomimetic of at least 6 amino acids in length, but not more than 8 amino acids in length, comprising a motif having the sequence: KSEVSK (SEQ ID NO: 3), wherein the modified peptide:
comprises a protecting group, wherein the modified peptide has improved ex vivo and/or in vivo peptide stability and/or improved skin penetration when administered topically, relative to an unmodified peptide of the same sequence; or
is functionalized with a polymer selected from the group consisting of a polyethylene glycol, a cellulose, and a modified cellulose, wherein the modified peptide has increased bioavailability, relative to an unmodified peptide of the same sequence; and
wherein the peptidomimetic comprises one or more peptide linkages replaced with a linkage selected from the group consisting of —CH 2 NH—, —CH 2 S—, —CH 2 —CH 2 —, —CH═CH—, —COCH 2 —, —CH(OH)CH 2 —, and —CH 2 SO, wherein the peptidomimetic has an improvement in a property, relative to an unmodified peptide of the same sequence, wherein the property is selected from the group consisting of: economy of production, chemical stability, half-life, absorption, potency, efficacy, and/or reduced antigenicity.
16. The modified peptide or peptidomimetic of claim 15 , wherein the modified peptide or peptidomimetic is 6 amino acids in length.
17. The modified peptide or peptidomimetic of claim 15 , which is a modified peptide comprising a protecting group, wherein the modified peptide has improved ex vivo and/or in vivo peptide stability and/or improved skin penetration when administered topically, relative to an unmodified peptide of the same sequence.
18. The modified peptide or peptidomimetic of claim 17 , wherein the protecting group comprises an acetyl group at the amino-terminus of the peptide or peptidomimetic.
19. The modified peptide or peptidomimetic of claim 15 , which is a modified peptide functionalized with a polymer selected from the group consisting of a polyethylene glycol, a cellulose, and a modified cellulose, wherein the modified peptide has increased bioavailability, relative to an unmodified peptide of the same sequence.
20. The modified peptide or peptidomimetic of claim 15 , which is a peptidomimetic comprising one or more peptide linkages replaced with a linkage selected from the group consisting of —CH 2 NH—, —CH 2 S—, —CH 2 —CH 2 —, —CH═CH—, —COCH 2 —, —CH(OH)CH 2 —, and —CH 2 SO, wherein the peptidomimetic has an improvement in a property, relative to an unmodified peptide of the same sequence, wherein the property is selected from the group consisting of: economy of production, chemical stability, half-life, absorption, potency, efficacy, and/or reduced antigenicity.
21. A method of stimulating adipogenesis in a subject, the method comprising administering the composition of claim 1 to the skin of a subject in an amount sufficient to stimulate adipogenesis.
22. The method of claim 21 , wherein the skin comprises a burn scar, a surgical scar, an acne scar, a biopsy scar, or scarring produced by an injury.
23. The method of claim 21 , wherein the subject is a human.
24. A method of stimulating adipogenesis in a subject, the method comprising administering the composition of claim 1 subcutaneously to a subject in an amount sufficient to stimulate adipogenesis.
25. The method of claim 24 , wherein the composition is administered subcutaneously to a lip, an eye lid, a cheek, a forehead, a chin, or a neck.
26. The method of claim 24 , wherein the subject is human.