Tribonectins
The invention features a tribonectin and a method of tribosupplementation carried out by administering tribonectins directly to an injured or arthritic joint.
1. An isolated tribonectin polypeptide having a molecular weight of 280 kDa or less and comprising an amino acid sequence that comprises a multiplicity of subunits, wherein
(a) each subunit comprises at least seven amino acids;
(b) each subunit comprises at least one threonine and has an amino acid sequence that is at least 50% identical to SEQ ID NO: 3, wherein a non-identical amino acid is a conservative amino acid substitution; and one or more of said subunits comprising an O-linked β(1-3) Gal-GaINAc oligosaccharide.
2. The tribonectin of claim 1 , wherein the amino acid sequence of said subunit is SEQ ID NO: 3.
3. The tribonectin of claim 1 , wherein said tribonectin further comprises one or more repeats of the amino acid sequence of SEQ ID NO: 4.
4. The tribonectin of claim 1 , wherein said tribonectin comprises an amino acid sequence that is at least 85% identical to amino acids 200-1140, inclusive, of the amino acid sequence of SEQ ID NO: 1.
5. The tribonectin of claim 4 , wherein said tribonectin reduces the coefficient of friction between bearing articular cartilage surfaces.
6. The tribonectin of claim 4 , wherein said tribonectin reduces the coefficient of friction between bearing surfaces in vitro.
7. The tribonectin of claim 4 , wherein said tribonectin reduces the coefficient of friction between bearing surfaces in vivo.
8. The tribonectin of claim 4 , wherein said tribonectin does not substantially increase the viscosity of a solution to which it is added.
9. The tribonectin of claim 1 , wherein the molecular weight of said tribonectin is in the range of 220-280 kDa.
10. The tribonectin of claim 1 , wherein said tribonectin comprises a fragment of megakaryocyte stimulating factor.
11. The tribonectin of claim 4 , wherein said tribonectin comprises an amino acid sequence that is at least 95% identical to amino acids 200-1140, inclusive, of the amino acid sequence of SEQ ID NO: 1
12. The tribonectin of claim 11 , wherein said tribonectin comprises an amino acid sequence that is at least 98% identical to amino acids 200-1140, inclusive, of the amino acid sequence of SEQ ID NO: 1.
13. The tribonectin of claim 12 , wherein said tribonectin comprises the amino acid sequence of residues 200-1140, inclusive, of the amino acid sequence of SEQ ID NO: 1.
14. The tribonectin of claim 4 , wherein said tribonectin comprises an amino acid sequence that is at least 95 % identical to amino acids 200-1167, inclusive, of the amino acid sequence of SEQ ID NO: 1.
15. The tribonectin of claim 14 , wherein said tribonectin comprises the amino acid sequence of residues 200-1167, inclusive, of the amino acid sequence of SEQ ID NO: 1.
16. The tribonectin of claim 4 , wherein said tribonectin comprises an amino acid sequence that is at least 95% identical to amino acids 200-1212, inclusive, of the amino acid sequence of SEQ ID NO: 1.
17. The tribonectin of claim 16 , wherein said tribonectin comprises the amino acid sequence of residues 200-1212, inclusive, of the amino acid sequence of SEQ ID NO: 1.
18. The tribonectin of claim 4 , wherein said tribonectin comprises an amino acid sequence that is at least 95% identical to amino acids 200-1263, inclusive, of the amino acid sequence of SEQ ID NO: 1.
19. The tribonectin of claim 18 , wherein said tribonectin comprises the amino acid sequence of residues 200-1263, inclusive, of the amino acid sequence of SEQ ID NO: 1.
20. The tribonectin of claim 4 , wherein said tribonectin lacks the amino acid sequence of residues 1-24, inclusive, of SEQ ID NO: 1.
21. The tribonectin of claim 4 , wherein said tribonectin lacks the amino acid sequence of residues 67-104, inclusive of SEQ ID NO: 1.
22. The tribonectin of claim 1 , wherein said tribonectin lubricates a mammalian joint.
23. The tribonectin of claim 22 , wherein said joint is an articulating joint of a human, dog, or horse.
24. The tribonectin of claim 1 , wherein said tribonectin inhibits tissue adhesion formation in a mammal.
25. The tribonectin of claim 1 , wherein the β(1-3) Gal-GalNAc moiety further comprises a sialic acid (NeuAc) cap.
26. A composition comprising the tribonectin of claim 1 and a pharmaceutically acceptable carrier.
27. The composition of claim 26 , wherein said composition is in the form of a membrane, foam, gel, or fiber.
28. The composition of claim 26 , wherein said composition is formulated for timed release of said tribonectin.
29. The composition of claim 26 further comprising hyaluronic acid.
30. The composition of claim 26 , wherein said composition comprises 20 to 500 μg/mL of said tribonectin in a volume of about 0.1 to 2 mL, wherein said composition is formulated for injection.
31. The composition of claim 26 , wherein said composition comprises 250 μg/mL of said tribonectin.
32. The tribonectin of claim 1 , wherein one or more of said subunits comprises a covalent, non-peptide bond.
33. A composition comprising the tribonectin of claim 32 and a pharmaceutically acceptable carrier.
34. The composition of claim 1 , wherein said composition comprises fewer than 76 of said subunits.