Peptides, compositions, and methods for stimulating subcutaneous adipogenesis
Peptides that stimulate subcutaneous adipogenesis in mammals and uses thereof are provided.
1. A modified peptide or peptidomimetic having a length of 10 to 14 amino acids and comprising the sequence (III):
Z1-Z2-Z3-Z4-Z5-Z6-Z7-Z8-Z9-Z10 (III)
wherein:
Z1 is lysine (K) or alanine (A);
Z2 is leucine (L), isoleucine (I), or alanine (A);
Z3 is lysine (K) or alanine (A);
Z4 is aspartic acid (D), threonine (T), or alanine (A);
Z5 is glutamic acid (E);
Z6 is asparagine (N)
Z7 is serine (S) or alanine (A);
Z8 is glutamine (Q);
Z9 is leucine (L); and
Z10 is lysine (K), arginine (R), or alanine (A);
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 modified peptide or peptidomimetic of claim 1 , 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.
3. The modified peptide or peptidomimetic of claim 1 , 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.
4. The modified peptide or peptidomimetic of claim 1 , 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.
5. A pharmaceutical or cosmetic composition comprising:
the modified peptide or peptidomimetic of claim 1 ; and
a pharmaceutically or cosmetically acceptable carrier.
6. The composition of claim 5 , wherein the composition is for topical administration, subcutaneous administration, transdermal administration, or injection.
7. The composition of claim 5 , wherein the composition further comprises collagen and/or an anesthetic.
8. The modified peptide or peptidomimetic of claim 1 , wherein the amino acid sequence of the modified peptide or peptidomimetic comprises KIKDENSQLK (SEQ ID NO: 92).
9. The modified peptide or peptidomimetic of claim 1 , wherein the amino acid sequence of the modified peptide or peptidomimetic comprises ALKDENSQLK (SEQ ID NO: 90).
10. The modified peptide or peptidomimetic of claim 1 , wherein the amino acid sequence of the modified peptide or peptidomimetic comprises KLADENSQLK (SEQ ID NO: 91).
11. The modified peptide or peptidomimetic of claim 1 , wherein the amino acid sequence of the modified peptide or peptidomimetic comprises KAKDENSQLR (SEQ ID NO: 98).
12. The modified peptide or peptidomimetic of claim 1 , wherein the amino acid sequence of the modified peptide or peptidomimetic comprises KLKAENSQLR (SEQ ID NO: 100).
13. The modified peptide or peptidomimetic of claim 1 , wherein the amino acid sequence of the modified peptide or peptidomimetic comprises KLKDENAQLR (SEQ ID NO: 103).
14. The modified peptide or peptidomimetic of claim 1 , wherein the amino acid sequence of the modified peptide or peptidomimetic comprises KLKDENSQLA (SEQ ID NO: 106).
15. The modified peptide or peptidomimetic of claim 1 , wherein the amino acid sequence of the modified peptide or peptidomimetic comprises KLKTENSQLK (SEQ ID NO: 95).
16. The modified peptide or peptidomimetic of claim 1 , wherein the modified peptide or peptidomimetic is capable of stimulating subcutaneous adipogenesis.
17. A method of stimulating adipogenesis in a subject, the method comprising administering the modified peptide or peptidomimetic of claim 1 topically to a subject in an amount sufficient to stimulate adipogenesis.
18. A method of stimulating adipogenesis in a subject, the method comprising administering the modified peptide or peptidomimetic of claim 1 subcutaneously to a subject in an amount sufficient to stimulate adipogenesis.
19. A method of stimulating adipogenesis in a subject, the method comprising administering the modified peptide or peptidomimetic of claim 1 transdermally to the subject in an amount sufficient to stimulate adipogenesis.
20. The method of claim 17 , wherein the subject is human.
21. The method of claim 18 , wherein the subject is human.
22. The method of claim 19 , wherein the subject is human.