Plant-derived elastin binding protein ligands and methods of using the same

Abstract

The present invention describes novel plant derived elastin-like peptides and peptidomimetics that may serve as functional ligands for elastin receptors and stimulate elastogenesis. The novel plant derived peptides provide an alternative (non-animal derived) source of GXXPG (SEQ ID NO. 2) containing peptides. The present invention also describes therapeutic compositions containing novel plant derived peptides or peptidomimetics useful in stimulating elastogenensis and capillary dilatation. The therapeutic compositions of the present invention that comprise novel plant derived peptides or peptidomimetics may be combined with other therapeutic agents.

What is claimed is: 
     
         1 . A synthetic sextapeptide comprising the sequence X 1 -X 2 -X 3 -X 4 -X 5 -X 6  (SEQ ID NO: 17), wherein:
 X 1  is a mimetic of V or a mimetic of I;   X 2  is a mimetic of G;   X 3  is a mimetic of A or a mimetic of L;   X 4  is a mimetic of M or a mimetic of S;   X 5  is a mimetic of P; and   X 6  is a mimetic of G.   
     
     
         2 . The synthetic sextapeptide of  claim 1 , wherein the mimetic amino acid has one or more side chains replaced with a side chain selected from the group consisting of alkyl, lower alkyl, cyclic 4-membered alkyl, cyclic 5-membered alkyl, cyclic 6-membered alkyl, cyclic 7-membered alkyl, amide, amide lower alkyl, amide di (lower alkyl), lower alkoxy, hydroxy, carboxy and the lower ester derivatives thereof, and 4-membered heterocyclics, 5-membered heterocyclics, 6-membered heterocyclics, to 7-membered heterocyclics. 
     
     
         3 . A composition comprising the synthetic sextapeptide of  claim 1 . 
     
     
         4 . The composition of  claim 3 , further comprising a manganese compound, a trivalent iron compound, a sodium compound, a copper compound, an antioxidant, an additive, an excipient, or a combination thereof. 
     
     
         5 . The composition of  claim 3 , wherein the composition stimulates elastogenesis. 
     
     
         6 . The composition of  claim 3 , wherein the composition is used to enhance wound healing or treat cutaneous hypertrophic scars. 
     
     
         7 . The composition of  claim 6 , wherein the composition is applied to the skin of a subject, and wherein the skin is selected from the group consisting of face, arms, legs, chest, and neck. 
     
     
         8 . The composition of  claim 3 , wherein the composition is a solution, a cream, an emulsion, a gel, a solid, or an aerosol. 
     
     
         9 . A synthetic acetylated sextapeptide comprising the sequence X 1 -X 2 -X 3 -X 4 -X 5 -X 6  (SEQ ID NO: 3), wherein:
 X 1  is a V or I;   X 2  is G;   X 3  is A or L;   X 4  is M or S;   X 5  is P; and   X 6  is G, and   wherein acetylation is at N-terminus.   
     
     
         10 . The synthetic acetylated sextapeptide of  claim 9 , wherein the synthetic acetylated sextapeptide is selected from the group consisting of acetylated VGAMPG (SEQ ID NO. 4), acetylated VGLSPG (SEQ ID NO. 5), acetylated IGAMPG (SEQ ID NO. 6), and acetylated IGLSPG (SEQ ID NO. 7). 
     
     
         11 . A composition comprising the synthetic acetylated sextapeptide of  claim 9 . 
     
     
         12 . The composition of  claim 11 , further comprising a manganese compound, a trivalent iron compound, a sodium compound, a copper compound, an antioxidant, an additive, an excipient, or a combination thereof. 
     
     
         13 . The composition of  claim 11 , wherein the composition stimulates elastogenesis. 
     
     
         14 . The composition of  claim 11 , wherein the composition is used to enhance wound healing or treat cutaneous hypertrophic scars. 
     
     
         15 . The composition of  claim 14 , wherein the composition is applied to the skin of a subject, and wherein the skin is selected from the group consisting of face, arms, legs, chest, and neck. 
     
     
         16 . The composition of  claim 11 , wherein the composition is a solution, a cream, an emulsion, a gel, a solid, or an aerosol. 
     
     
         17 . A synthetic linked sextapeptide comprising the sequence X 1 -X 2 -X 3 -X 4 -X 5 -X 6 -X 7 -X 1 -X 2 -X 3 -X 4 -X 5 -X 6  (SEQ ID NO: 18), wherein:
 X 1  is a mimetic of V or a mimetic of I;   X 2  is a mimetic of G;   X 3  is a mimetic of A or a mimetic of L;   X 4  is a mimetic of M or a mimetic of S;   X 5  is a mimetic of P;   X 6  is a mimetic of G; and   X 7  is a linking moiety.   
     
     
         18 . The synthetic linked sextapeptide of  claim 17 , wherein the mimetic amino acid has one or more side chains replaced with a side chain selected from the group consisting of alkyl, lower alkyl, cyclic 4-membered alkyl, cyclic 5-membered alkyl, cyclic 6-membered alkyl, cyclic 7-membered alkyl, amide, amide lower alkyl, amide di (lower alkyl), lower alkoxy, hydroxy, carboxy and the lower ester derivatives thereof, and 4-membered heterocyclics, 5-membered heterocyclics, 6-membered heterocyclics, to 7-membered heterocyclics. 
     
     
         19 . The synthetic linked sextapeptide of  claim 17 , wherein the linking moiety is selected from the group consisting of an amino acid, alanine, a disulfide bond, a carbonyl moiety, a hydrocarbon moiety optionally substituted at one or more available carbon atoms with a lower alkyl substituent, a lysine residue, and a lysine amide. 
     
     
         20 . A composition comprising the synthetic linked sextapeptide of  claim 17 . 
     
     
         21 . The composition of  claim 20 , further comprising a manganese compound, a trivalent iron compound, a sodium compound, a copper compound, an antioxidant, an additive, an excipient, or a combination thereof. 
     
     
         22 . The composition of  claim 20 , wherein the composition stimulates elastogenesis. 
     
     
         23 . The composition of  claim 20 , wherein the composition is used to enhance wound healing or treat cutaneous hypertrophic scars. 
     
     
         24 . The composition of  claim 23 , wherein the composition is applied to the skin of a subject, and wherein the skin is selected from the group consisting of face, arms, legs, chest, and neck. 
     
     
         25 . The composition of  claim 20 , wherein the composition is a solution, a cream, an emulsion, a gel, a solid, or an aerosol. 
     
     
         26 . A synthetic linked acetylated sextapeptide comprising the sequence X 1 -X 2 -X 3 -X 4 -X 5 -X 6 -X 7 -X 1 -X 2 -X 3 -X 4 -X 5 -X 6  (SEQ ID NO: 16), wherein:
 X 1  is a V or I;   X 2  is G;   X 3  is A or L;   X 4  is M or S;   X 5  is P;   X 6  is G, and   X 7  is a linking moiety; and   wherein acetylation is at N-terminus.   
     
     
         27 . The synthetic linked acetylated sextapeptide of  claim 26 , wherein the synthetic acetylated sextapeptide is selected from the group consisting of acetylated VGAMPGAAAAAVGAMPG (SEQ ID NO. 8), acetylated VGLSPGAAAAAVGLSPG (SEQ ID NO. 9), acetylated VGVAPGAAAAAVGVAPG (SEQ ID NO. 10), acetylated IGAMPGAAAAAIGAMPG (SEQ ID NO. 11), acetylated IGLSPGAAAAAIGLSPG (SEQ ID NO. 12), and acetylated IGVAPGAAAAAIGVAPG (SEQ ID NO. 14). 
     
     
         28 . A composition comprising the synthetic linked acetylated sextapeptide of  claim 26 . 
     
     
         29 . The composition of  claim 28 , further comprising a manganese compound, a trivalent iron compound, a sodium compound, a copper compound, an antioxidant, an additive, an excipient, or a combination thereof. 
     
     
         30 . The composition of  claim 28 , wherein the composition stimulates elastogenesis. 
     
     
         31 . The composition of  claim 28 , wherein the composition is used to enhance wound healing or treat cutaneous hypertrophic scars. 
     
     
         32 . The composition of  claim 31 , wherein the composition is applied to the skin of a subject, and wherein the skin is selected from the group consisting of face, arms, legs, chest, and neck. 
     
     
         33 . The composition of  claim 28 , wherein the composition is a solution, a cream, an emulsion, a gel, a solid, or an aerosol.