CC-chemokine binding tick proteins
View Patent ↗A novel CC-chemokine binding protein is isolated from the saliva of Rhipicephalus sanguineus . Compounds prepared in accordance with the present invention can be used as anti-inflammatory compounds and in the treatment or prevention of CC-chemokine-related diseases.
1. A composition of matter comprising:
a) an isolated polypeptide comprising:
i) SEQ ID NO: 4;
ii) SEQ ID NO: 6; or
iii) a fusion protein comprising SEQ ID NO: 4 or SEQ ID NO: 6 fused to a heterologous sequence selected from: an extracellular domain of a membrane-bound protein, an immunoglobulin constant region, a multimerization domain, a heterodimeric protein hormone, a signal peptide, an export signal, or a tag sequence;
b) an isolated polynucleotide:
A) encoding a polypeptide, said polypeptide comprising:
i) SEQ ID NO: 4;
ii) SEQ ID NO: 6; or
iii) a fusion protein comprising SEQ ID NO: 4 or SEQ ID NO: 6 fused to a heterologous sequence selected from: an extracellular domain of a membrane-bound protein, an immunoglobulin constant region, a multimerization domain, a heterodimeric protein hormone, a signal peptide, an export signal, or a tag sequence;
B) comprising SEQ ID NO: 3; or
C) comprising SEQ ID NO: 5;
c) a vector comprising a polynucleotide:
A) encoding a polypeptide comprising:
i) SEQ ID NO: 4;
ii) SEQ ID NO: 6; or
iii) a fusion protein comprising SEQ ID NO: 4 or SEQ ID NO: 6 fused to a heterologous sequence selected from: an extracellular domain of a membrane-bound protein, an immunoglobulin constant region, a multimerization domain, a heterodimeric protein hormone, a signal peptide, an export signal, or a tag sequence;
B) comprising SEQ ID NO: 3; or
C) comprising SEQ ID NO: 5; or
d) an isolated host cell transformed or transfected with an expression vector comprising a polynucleotide:
A) encoding a polypeptide comprising:
i) SEQ ID NO: 4;
ii) SEQ ID NO: 6; or
iii) a fusion protein comprising SEQ ID NO: 4 or SEQ ID NO: 6 fused to a heterologous sequence selected from: an extracellular domain of a membrane-bound protein, an immunoglobulin constant region, a multimerization domain, a heterodimeric protein hormone, a signal peptide, an export signal, or a tag sequence;
B) comprising SEQ ID NO: 3; or
C) comprising SEQ ID NO: 5.
2. The composition of matter according to claim 1 , wherein said composition of matter is a polypeptide that is post-translationally modified.
3. The composition of matter according to claim 2 , wherein said composition of matter is a polypeptide that is glycosylated.
4. The composition of matter according to claim 1 , wherein said composition of matter is a polypeptide that is PEGylated.
5. The composition of matter according to claim 1 , wherein said composition of matter is an isolated polypeptide comprising SEQ ID NO: 4.
6. The composition of matter according to claim 1 , wherein said composition of matter is an isolated polypeptide comprising SEQ ID NO: 6.
7. The composition of matter according to claim 1 , wherein said composition of matter is an isolated polypeptide comprising a fusion protein comprising SEQ ID NO: 4 or SEQ ID NO: 6 fused to a heterologous sequence selected from: an extracellular domain of a membrane-bound protein, an immunoglobulin constant region, a multimerization domain, a heterodimeric protein hormone, a signal peptide, an export signal, or a tag sequence.
8. The composition of matter according to claim 1 , wherein said composition of matter is an isolated polynucleotide encoding a polypeptide comprising SEQ ID NO: 4.
9. The composition of matter according to claim 1 , wherein said composition of matter is an isolated polynucleotide encoding a polypeptide comprising SEQ ID NO: 6.
10. The composition of matter according to claim 1 , wherein said composition of matter is an isolated polynucleotide encoding a polypeptide comprising a fusion protein comprising SEQ ID NO: 4 or SEQ ID NO: 6 fused to a heterologous sequence selected from: an extracellular domain of a membrane-bound protein, an immunoglobulin constant region, a multimerization domain, a heterodimeric protein hormone, a signal peptide, an export signal, or a tag sequence.
11. The composition of matter according to claim 1 , wherein said composition of matter is an isolated polynucleotide comprising SEQ ID NO: 3.
12. The composition of matter according to claim 1 , wherein said composition of matter is an isolated polynucleotide comprising SEQ ID NO: 5.
13. The composition of matter according to claim 1 , wherein said composition of matter is a vector comprising a polynucleotide, said polynucleotide encoding a polypeptide comprising SEQ ID NO: 4.
14. The composition of matter according to claim 1 , wherein said composition of matter is a vector comprising a polynucleotide, said polynucleotide encoding a polypeptide comprising SEQ ID NO: 6.
15. The composition of matter according to claim 1 , wherein said composition of matter is a vector comprising a polynucleotide, said polynucleotide encoding a polypeptide comprising a fusion protein comprising SEQ ID NO: 4 or SEQ ID NO: 6 fused to a heterologous sequence selected from: an extracellular domain of a membrane-bound protein, an immunoglobulin constant region, a multimerization domain, a heterodimeric protein hormone, a signal peptide, an export signal, or a tag sequence.
16. The composition of matter according to claim 1 , wherein said composition of matter is a vector comprising SEQ ID NO: 3.
17. The composition of matter according to claim 1 , wherein said composition of matter is a vector comprising SEQ ID NO: 5.
18. The composition of matter according to claim 1 , wherein said composition of matter is an isolated host cell transformed or transfected with an expression vector comprising a polynucleotide encoding SEQ ID NO: 4.
19. The composition of matter according to claim 1 , wherein said composition of matter is an isolated host cell transformed or transfected with an expression vector comprising a polynucleotide encoding SEQ ID NO: 6.
20. The composition of matter according to claim 1 , wherein said composition of matter is an isolated host cell transformed or transfected with an expression vector comprising a polynucleotide encoding a polypeptide comprising a fusion protein comprising SEQ ID NO: 4 or SEQ ID NO: 6 fused to a heterologous sequence selected from: an extracellular domain of a membrane-bound protein, an immunoglobulin constant region, a multimerization domain, a heterodimeric protein hormone, a signal peptide, an export signal, or a tag sequence.
21. The composition of matter according to claim 1 , wherein said composition of matter is an isolated host cell transformed or transfected with an expression vector comprising SEQ ID NO: 3.
22. The composition of matter according to claim 1 , wherein said composition of matter is an isolated host cell transformed or transfected with an expression vector comprising SEQ ID NO: 5.
23. A process for preparing a polypeptide comprising culturing a transformed or transfected host cell under conditions allowing or promoting expression of a polypeptide, said host cell comprising:
a) a polynucleotide encoding a polypeptide selected from:
i) SEQ ID NO: 4;
ii) SEQ ID NO: 6;
iii) a fusion protein comprising SEQ ID NO: 4 or SEQ ID NO: 6 fused to a heterologous sequence selected from: an extracellular domain of a membrane-bound protein, an immunoglobulin constant region, a multimerization domain, a heterodimeric protein hormone, a signal peptide, an export signal, or a tag sequence;
b) a polynucleotide comprising SEQ ID NO: 3; or
c) a polynucleotide comprising SEQ ID NO: 5.
24. The process according to claim 23 , further comprising purifying the polypeptide.
25. The process according to claim 24 , further comprising formulating the polypeptide into a composition.
26. A method of inhibiting TNF-α release by monocytes comprising contacting monocytes with a composition comprising a carrier and a polypeptide comprising SEQ ID NO: 4 or SEQ ID NO: 6.
27. The method according to claim 26 , wherein said polypeptide is SEQ ID NO: 6.
28. The method according to claim 26 , wherein said polypeptide comprises SEQ ID NO: 4.