Synthetic peptide and peptide conjugates and related tissue coupling methods via transglutaminase enzyme
Peptides and conjugates thereof comprising one or more bioactive agents which can be coupled to a tissue via a transglutaminase and related methods.
1. A peptide conjugate compound comprising a bioactive agent, said agent a prodrug of a glucocorticoid; a peptide component comprising at least one of a lysinyl and a glutaminyl substrate for a transglutaminase; a component coupling said agent to said peptide, said coupling component cleavable under physiological conditions; and a terminal linear monomethoxy poly(ethylene) glycol component coupled to said peptide component.
2. The compound of claim 1 wherein said peptide component comprises a sequence comprising at least one of FKG and GQQQLG (SEQ ID NO: 1).
3. The compound of claim 1 wherein said coupling moiety is hydrolysable.
4. The compound of claim 3 wherein said coupling component comprises an ester moiety.
5. The compound of claim 1 wherein said agent is a prodrug of hydrocortisone.
6. The compound of claim 1 coupled to a substrate comprising an extracellular matrix component.
7. The compound of claim 6 coupled to one of a cartilage tissue and a meniscus tissue.
8. A peptide conjugate compound comprising a prodrug of hydrocortisone; a peptide component comprising at least one of a lysinyl and a glutaminyl substrate for a transglutaminase; a component coupling said prodrug to said peptide, said coupling component cleavable under physiological conditions; and a terminal linear monomethoxy poly(ethylene) glycol component coupled to said peptide component.
9. The compound of claim 8 wherein said coupling component comprises an ester moiety.
10. The compound of claim 8 wherein said peptide component comprises a sequence comprising at least one of FKG and GQQQLG (SEQ ID NO: 1).
11. The compound of claim 8 coupled to one of a cartilage tissue and a meniscus tissue.
12. A composition comprising a compound selected from a peptide conjugate compound of claim 1 and a pharmaceutically-acceptable salt thereof; and a pharmaceutically-acceptable carrier.
13. The compound of claim 12 wherein said peptide component comprises a sequence comprising at least one of FKG and GQQQLG (SEQ ID NO: 1).
14. The composition of claim 12 wherein said coupling moiety is hydrolysable.
15. The composition of claim 12 wherein said agent is a prodrug of a glucocorticoid.
16. The composition of claim 15 wherein said agent is a prodrug of hydrocortisone.
17. The composition of claim 12 coupled to a tissue substrate comprising an extracellular matrix component.
18. A peptide conjugate compound comprising a bioactive agent selected from a glucocorticoid and a prodrug of a glucocorticoid; a peptide component comprising a lysinyl substrate for a transglutaminase, said substrate comprising a GFKG sequence; and a component coupling said agent to said peptide, said coupling component cleavable under physiological conditions.
19. The compound of claim 18 wherein said agent is a prodrug of a glucocorticoid.
20. The compound of claim 18 comprising a terminal linear monomethoxy poly(ethylene) glycol component coupled to said peptide component.