Molecules for transporting a compound across the blood-brain barrier
The invention relates to improvements in the field of drug delivery. More particularly, the invention relates to polypeptide derived from aprotinin and from aprotinin analogs as well as conjugates and pharmaceutical compositions comprising these polypeptides. The present invention also relates to the use of these polypeptide for transporting a compound or drug across the blood-brain barrier of an individual and in the treatment and diagnosis of neurological diseases.
1. A composition comprising a polypeptide, said polypeptide comprising the amino acid sequence of SEQ ID NO:97 , wherein said polypeptide is capable of crossing the blood-brain barrier (BBB) in situ or an in vitro model of the BBB that is a co-culture of astrocytes and bovine brain capillary endothelial cells.
2. The composition of claim 1 , wherein said polypeptide is from 19 to 50 amino acids long.
3. The composition of claim 2 , further comprising a pharmaceutically acceptable carrier.
4. The composition of claim 2 , wherein said polypeptide is produced by chemical synthesis.
5. The composition of claim 2 , wherein said polypeptide is produced recombinantly.
6. The composition of claim 1 , wherein said amino acid sequence consists of the sequence of SEQ ID NO:97.
7. The composition of claim 1 , further comprising a pharmaceutically acceptable carrier.
8. The composition of claim 1 , wherein said polypeptide is produced by chemical synthesis.
9. The composition of claim 1 , wherein said polypeptide is produced recombinantly.
10. A compound comprising:
(a) a therapeutic agent; and
(b) a polypeptide comprising the amino acid sequence of SEQ ID NO:97wherein said polypeptide is conjugated to said therapeutic agent and said polypeptide is capable of crossing the blood-brain barrier in situ or an in vitro model of the blood-brain barrier that is a co-culture of astrocytes and bovine brain capillary endothelial cells.
11. The compound of claim 10 , wherein said polypeptide consists of the sequence of SEQ ID NO:97.
12. A composition comprising the compound of claim 10 , and a pharmaceutically acceptable carrier.
13. The compound of claim 10 , wherein said therapeutic agent is an anticancer agent.
14. The compound of claim 13 , wherein said anticancer agent is a small molecule drug is selected from the group consisting of paclitaxel, vinblastine, vincristine, etoposide, doxorubicin, cyclophosphamide, taxotere, meiphalan, and chlorambucil, or a combination thereof.
15. The compound of claim 14 , wherein said small molecule drug is paclitaxel.
16. The compound of claim 15 , wherein said polypeptide consists of the sequence of SEQ ID NO:97.
17. A composition comprising the compound of claim 15 , and a pharmaceutically acceptable carrier.
18. The compound of claim 14 , wherein said anticancer agent is doxorubicin.
19. The compound of claim 18 , wherein said polypeptide consists of the sequence of SEQ ID NO:97.
20. A composition comprising the compound of claim 18 , and a pharmaceutically acceptable carrier.
21. The compound of claim 14 , wherein said anticancer agent is etoposide.
22. The compound of claim 21 , wherein said polypeptide consists of the sequence of SEQ ID NO:97.
23. A composition comprising the compound of claim 21 , and a pharmaceutically acceptable carrier.
24. The compound of claim 10 , wherein said compound is substantially pure.
25. The compound of claim 10 , wherein said polypeptide is produced by chemical synthesis.
26. The compound of claim 10 , wherein said polypeptide is produced recombinantly.
27. A compound comprising:
(a) a polypeptide comprising the amino acid sequence of SEQ ID NO:97; and
(b) paclitaxel, wherein said paclitaxel is conjugated to said polypeptide.
28. The compound of claim 27 , wherein three molecules of paclitaxel are conjugated to each molecule of said polypeptide.