Collagen-binding synthetic peptidoglycans, preparation, and methods of use
This invention relates to collagen-binding synthetic peptidoglycans and engineered collagen matrices comprising a collagen matrix and a collagen-binding synthetic peptidoglycan where the collagen-binding synthetic peptidoglycan can be aberrant or can have amino acid homology with a portion of the amino acid sequence of a protein or a proteoglycan that regulates collagen fibrillogenesis. The invention also relates to kits, compounds, compositions, and engineered graft constructs comprising such collagen-binding synthetic peptidoglycans or engineered collagen matrices and methods for their preparation and use.
1. A compound of formula (P n L) χ G wherein n is 1 to 5;
X is 1 to 10;
P is a synthetic peptide of up to about 40 amino acids comprising the amino acid sequence RRANAALKAGELYKSILYGC (SEQ ID NO: 1) wherein the amino acid sequence comprises a collagen-binding domain;
L is a linker which links “P” and “G” in said formula; and
G is a glycan, wherein P is linked to G via the linker.
2. The compound of claim 1 wherein the glycan is a glycosaminoglycan or a polysaccharide.
3. The compound of claim 1 wherein the glycan is selected from the group consisting of alginate, agarose, dextran, chondroitin, dermatan, dermatan sulfate, heparan, heparin, keratin, and hyaluronan.
4. The compound of claim 1 wherein the glycan is selected from the group consisting of dermatan sulfate, dextran, and heparin.
5. The compound of claim 1 wherein the linker is —SCH 2 CH 2 C(O)NHN═.
6. A composition comprising the compound of claim 1 and one or more pharmaceutically acceptable excipient, or diluent, or a combination thereof.
7. The composition of claim 6 in a form adapted for topical use.
8. The composition of claim 7 wherein the topical form is selected from the group consisting of a powder, a gel, a cream, an ointment, a plaster, and a topical liquid.
9. The composition of the claim 6 adapted for parenteral administration.
10. The composition of claim 9 wherein the parenteral administration is intravenous or intra-arterial.
11. The composition of claim 6 wherein the glycan is a glycosaminoglycan or a polysaccharide.
12. The composition of claim 6 wherein the glycan is selected from the group consisting of alginate, agarose, dextran, chondroitin, dermatan, dermatan sulfate, heparan, heparin, keratin, and hyaluronan.
13. The composition of claim 6 wherein the compound is formulated in a dose from 1 μg/kg to 10 mg/kg patient body weight for administration to a patient.
14. The composition of claim 6 wherein the compound is formulated in a dose from 100 μg/kg to about 1 mg/kg patient body weight for administration to a patient.
15. The composition of claim 6 wherein the compound is formulated in a dose from 1 μg/kg to about 500 μg/kg patient body weight for administration to a patient.
16. The composition of claim 6 wherein the compound is formulated in a dose from 100 μg/kg to about 400 μg/kg patient body weight for administration to a patient.