IGF-binding protein-derived peptide or small molecule
View Patent ↗New compositions based on IGF-binding protein sequences are provided. New tools for high-throughput research are provided. New methods for the treatment of human disease are provided. IGFBP-3-derived peptide or small molecule is administered to subjects having disease, thereby alleviating the symptoms of the disease.
1. A composition comprising an isolated MBD peptide, wherein said peptide is DKKGFYKKKQCRPSKGRKRGFCW (SEQ ID NO:1) or QCRPSKGRKRCGFCW (SEQ ID NO:3).
2. The composition of claim 1 , wherein said peptide is DKKGFYKKKQCRPSKGRKRGFCW (SEQ ID NO:1).
3. The composition of claim 1 , wherein said peptide is QCRPSKGRKRGFCW (SEQ ID NO:3).
4. A composition comprising an isolated MBD peptide, wherein said peptide comprises a sequence selected from the group consisting of QCRPSKGRKRGFCWAVDKYG (SEQ ID NO:37) and KKGFYKKKQCRPSKGRKRGFCWAVDKYG (SEQ ID NO:38).
5. The composition of claim 4 , wherein said MBD peptide comprises the sequence QCRPSKGRKRGFCWAVDKYG (SEQ ID NO:37).
6. The composition of claim 4 , wherein said MBD peptide comprises the sequence KKGFYKKKQCRPSKGRKRGFCWAVDKYG (SEQ ID NO:38).
7. A method for alleviating a symptom of a cancer, comprising administering an effective amount of an isolated MBD peptide to an individual suffering from said cancer, wherein said MBD peptide is a peptide selected from the group consisting of QCRPSKGRKRGFCW (SEQ ID NO:3), QCRPSKGRKRGFCWAVDKYG (SEQ ID NO:37), and KKGFYKKKQCRPSKGRKRGFCWAVDKYG (SEQ ID NO:38).
8. The method of claim 7 , wherein the cancer is selected from the group consisting of breast, prostate, colon, ovarian, pancreatic, gastric and lung cancer.
9. The method of claim 7 , wherein a co-administered agent is administered to the individual.
10. The method of claim 9 , wherein the co-administered agent is a chemical agent selected from the group consisting of doxorubicin, paclitaxel, methotrexate, tamoxifen, cyclophosphamide, vincristine, etoposide, streptozotocin and 5-fluorouracil.
11. The method of claim 10 , wherein said cancer is prostate cancer.
12. The method of claim 11 , wherein said co-administered agent is paclitaxel.
13. The method of claim 7 , wherein said MBD peptide is administered at about 0.001 to about 40 milligrams per kilogram total body weight per day (mg/kg/day).
14. The method of claim 7 , wherein said MBD peptide is QCRPSKGRKRGFCW (SEQ ID NO:3).
15. The method of claim 7 , wherein said MBD peptide is QCRPSKGRKRGFCWAVDKYG (SEQ ID NO:37.
16. The method of claim 7 , wherein said MBD peptide is KKGFYKKKQCRPSKGRKRGFCWAVDKYG (SEQ ID NO:38).
17. A method for intracellular delivery of a therapeutic molecule to cells of a subject, comprising:
administering a conjugate of an isolated MBD peptide and the therapeutic molecule to said subject, wherein said MBD peptide comprises cell internalization activity, and wherein said peptide is a peptide selected from the group consisting of DKKGFYKKKQCRPSKGRKRGFCW (SEQ ID NO:1), GFYKKKQCRPSKGRKRGFCW (SEQ ID NO:2), QCRPSKGRKRGFCW (SEQ ID NO:3), QCRPSKGRKRGFC (SEQ ID NO:8), CRPSKGRKRGFCW (SEQ ID NO:9), and CRPSKGRKRGFC (SEQ ID NO:4).
18. The method of claim 17 , wherein said MBD peptide is further linked to a caveolin consensus binding site.
19. The method of claim 17 , wherein said MBD peptide is DKKGFYKKKQCRPSKGRKRGFCW (SEQ ID NO:1).
20. The method of claim 17 , wherein said MBD peptide is GFYKKKQCRPSKGRKRGFCW (SEQ ID NO:2).
21. The method of claim 17 , wherein said MBD peptide is QCRPSKGRKRGFCW (SEQ ID NO:3).
22. The method of claim 17 , wherein said MBD peptide is QCRPSKGRKRGFC (SEQ ID NO:8).
23. The method of claim 17 , wherein said MBD peptide is CRPSKGRKRGFCW (SEQ ID NO:9).
24. The method of claim 17 , wherein said MBD peptide is CRPSKGRKRGFC (SEQ ID NO:4).
25. A method for intracellular delivery of a therapeutic molecule to cells of a subject, comprising:
administering a conjugate of an isolated MBD peptide and the therapeutic molecule to said subject, wherein said MBD peptide comprises cell internalization activity, and wherein said peptide comprises a sequence selected from the group consisting of QCRPSKGRKRGFCWAVDKYG (SEQ ID NO:37) and KKGFYKKKQCRPSKGRKRGFCWAVDKYG (SEQ ID NO:38).
26. The method of claim 25 , wherein said MBD peptide comprises the sequence QCRPSKGRKRGFCWAVDKYG (SEQ ID NO:37).
27. The method of claim 25 , wherein said MBD peptide comprises the sequence KKGFYKKKQCRPSKGRKRGFCWAVDKYG (SEQ ID NO:38).