Antiproliferative factor and methods of use
A novel antiproliferative factor comprising a glycopeptide is disclosed. In specific embodiments, the novel antiproliferative factor is associated with the bladder. Compositions, diagnostic kits and reagents, and methods of using the compounds for identifying and/or treating interstitial cystitis and cancer are disclosed.
1. A composition comprising a glycopeptide having one to six sugar moieties, wherein at least one sugar moiety is linked to
a) a peptide moiety comprises SEQ ID NO:10; or
b) a peptide moiety having one or two conservative substitutions in SEQ ID NO:10; or
c) a peptide moiety comprising SEQ ID NO:10 except that the first and second N-terminal amino acids are serine and leucine, respectively.
2. The composition of claim 1 , wherein one of the residues of the peptide is a linking amino acid that links the peptide to a sugar, and wherein the linking amino acid comprises a heteroatom covalently linked to one of the sugar moieties.
3. The composition of claim 2 , wherein the linking amino acid is a serine, threonine, or cysteine.
4. The composition of claim 2 , wherein the composition comprises two sugar residues and nine amino acids, wherein said linking amino acid is a serine, a threonine or a cysteine.
5. The composition of claim 1 , wherein the linkage between the sugar and the peptide is in the alpha or beta configuration.
6. The composition of claim 1 , wherein the linkage between the sugar and the peptide is in alpha configuration.
7. The composition of claim 1 , wherein the peptide moiety of b) comprises the same sequence as SEQ ID NO:3, SEQ ID NO:4, or SEQ ID NO:6, except that the proline is a D-proline.
8. The composition of claim 1 , wherein the conservative substitution comprises a hydrophobic conservative substitution.
9. The composition of claim 8 , wherein the hydrophobic conservative substitution comprises a substitution at one or more alanines, one or more valines, a proline; or a combination thereof.
10. The composition of claim 1 , wherein the composition comprises:
(a) Sialic acid-galactose-Nacetylgalactosamine-threonine-valine-D-proline-alanine-alanine-valine-valine-v aline-alanine;
(b) Sialic acid-galacto se-Nacetylglucosamine-threonine-valine -D-proline- alanine-alanine-valine -valine-valine-alanine; or
(c) Sialic acid-galactose-Nacetylglucosamine- serine-leucine-D-proline-alanine-alanine-valine -valine-valine-alanine.
11. The composition of (a) in claim 10 , further defined as having one or more of the following:
the sialic acid is linked to galactose via a 2,3 linkage;
the galactose is linked to the N-acetylgalactosamine via a 1,3 linkage; or
the N-acetyl galactosamine is linked to threonine via an 0 linkage in an alpha configuration.
12. The composition of (b) in claim 10 , further defined as having one or more of the following:
the sialic acid is linked to galactose via a 2,3 linkage; the galactose is linked to the N-acetylglucosamine via a 1,4 linkage; or the N-acetyl glucosamine is linked to threonine via an 0 linkage in an alpha configuration.
13. The composition of (c) in claim 10 , further defined as having one or more of the following:
the sialic acid is linked to galactose via a 2,3 linkage;
the galactose is linked to the N-acetylglucosamine via a 1,4 linkage; or
the N-acetylglucosamine is linked to serine via an 0 linkage in an alpha configuration.
14. The composition of claim 1 , further comprising a delivery vehicle.
15. The composition of claim 14 , wherein the delivery vehicle is a liposome, a cell, a conjugated molecule, a nanoparticle, or a mixture thereof.
16. The composition of claim 15 , wherein the conjugated molecule comprises an antibody, a peptide, folate, polyethylene glycol, a drug, a liposome, or lactosaminated human albumin.
17. The composition of claim 15 , wherein the nanoparticle comprises colloidal gold.
18. The composition of claim 1 comprised in a pharmaceutically acceptable excipient.
19. A composition comprising a glycopeptide, wherein the glycopeptide comprises two sugars and a peptide that comprises SEQ ID NO:10, wherein the sugars are β-galactose and N-acetyl galactosamine, wherein the N-acetyl galactosamine is linked to the peptide in the alpha configuration.
20. A kit, comprising the composition of claim 1 , wherein the composition is housed in a suitable container.
21. The composition of claim 1 , wherein the peptide comprises an amino acid mimetic.
22. The composition of claim 21 , wherein the amino acid mimetic is a mimetic of threonine, valine, alanine, serine, or leucine.
23. The composition of claim 19 , wherein the peptide comprises an amino acid mimetic.
24. The composition of claim 23 , wherein the amino acid mimetic is a mimetic of threonine, valine, alanine, serine, or leucine.
25. The kit of claim 20 , wherein the peptide comprises an amino acid mimetic.
26. The kit of claim 25 , wherein the amino acid mimetic is a mimetic of threonine, valine, alanine, serine, or leucine.