Claims
- 1. A peptide inhibitor for the binding of a circumsporozoite polypeptide to receptors of hepatocytes from malaria-susceptible mammals, said inhibitor having an amino acid sequence selected from the group consisting of:
(i) Region II+ of a circumsporozoite protein, said Region II+ containing the subsequence CSVTCG; (ii) fragments of said Region II+ containing at least a portion of the adhesion ligand for said receptors, said portion comprising at least one cysteine of said Region II+; (iii) peptide constructs comprising (a) (i) or (ii) and (b) at least one other fragment of the amino acid sequence of said circumsporozoite protein, said constructs having no substantial ability to elicit the formation of antibodies recognizing the immunodominant epitope of said circumsporozoite protein.
- 2. A peptide inhibitor for the binding of a circumsporozoite polypeptide to basolateral plasma membrane of hepatocytes from malaria-susceptible mammals, said inhibitor having an amino acid sequence selected from the group consisting of:
(i) Region II+ of a circumsporozoite protein, said Region II+ containing the subsequence CSVTCG; (ii) fragments of said Region II+ containing at least a portion of the adhesion ligand for said receptors, said portion comprising at least one cysteine of said Region II; (iii) peptide constructs comprising (a) (i) or (ii) and (b) at least one other fragment of the amino acid sequence of said circumsporozoite protein, said constructs having no substantial ability to elicit the formation of antibodies recognizing the immunodominant epitope of said circumsporozoite protein.
- 3. A method of inhibiting the binding of a circumsporozoite polypeptide to hepatocytes susceptible to sporozoite invasion, said method comprising:
supplying to the environment of said hepatocytes, the peptide inhibitor of claim 1 in an amount effective to inhibit said binding, no later than exposure of said hepatocytes to said circumsporozoite protein.
- 4. The method of claim 3, wherein said circumsporozoite polypeptide is native circumsporozoite protein present on the surface of viable, infectious malarial sporozoites.
- 5. The method of claim 3, wherein said circumsporozoite polypeptide is selected from the group consisting of native circumsporozoite protein, recombinant circumsporozoite protein, and recombinant fragments of circumsporozoite protein each comprising Region II+.
- 6. The method of claim 3, wherein said hepatocytes are human hepatocytes.
- 7. A peptide consisting essentially of Region II+ of the circumsporozoite protein.
- 8. The peptide of claim 7, said Region II+ being selected from the group consisting of
- 9. The peptide of claim 8, said peptide being P C S V T C G N G I Q V R I K P G S A.
- 10. The peptide of claim 7, said peptide being P C S V T C G N G I Q V R I K.
- 11. The peptide of claim 8, said peptide being P C S V T C G V G V R V R.
- 12. An inhibitor for the binding of a circumsporozoite polypeptide to a receptor of an hepatocyte from a malaria susceptible mammal, said inhibitor comprising a mimetic of the inhibitor of claim 1.
- 13. An inhibitor for the binding of a circumsporozoite polypeptide to a receptor of an hepatocyte from a malaria susceptible mammal, said inhibitor comprising a mimetic of the inhibitor of claim 2.
- 14. An inhibitor for the binding of a circumsporozoite polypeptide to a receptor of an hepatocyte from a malaria susceptible mammal, said inhibitor comprising a mimetic of the peptide of claim 7.
- 15. A method of inhibiting the binding of a circumsporozoite polypeptide to hepatocytes susceptible to sporozoite invasion, said method comprising:
supplying to the environment of said hepatocytes, the mimetic of claim 12 in an amount effective to inhibit said binding, no later than exposure of said hepatocytes to said circumsporozoite protein.
- 16. The method of claim 15, wherein said circumsporozoite polypeptide is native circumsporozoite protein present on the surface of viable, infectious malarial sporozoites.
- 17. The method of claim 15, wherein said circumsporozoite polypeptide is selected from the group consisting of native circumsporozoite protein, recombinant circumsporozoite protein, and recombinant fragments of circumsporozoite protein each comprising Region II+.
- 18. The method of claim 22, wherein said hepatocytes are human hepatocytes.
- 19. A method of delivering a substance to a hepatocyte in a mammal, said method comprising:
combining said substance with an inhibitor as defined in claim 1 to yield an inhibitor/substance complex; and administering said complex to said mammal.
- 20. The method of claim 19, wherein said substance comprises DNA.
- 21. The method of claim 19, wherein said substance comprises a pharmaceutically active compound.
- 22. A method of delivering a substance to a hepatocyte in a mammal, said method comprising:
combining said substance with an inhibitor as defined in claim 2 to yield an inhibitor/substance complex; and administering said complex to said mammal.
- 23. The method of claim 22, wherein said substance comprises DNA.
- 24. The method of claim 22, wherein said substance comprises a pharmaceutically active compound.
- 25. A method of delivering a substance to a hepatocyte in a mammal, said method comprising:
combining said substance with a peptide as defined in claim 7 to yield an inhibitor/substance complex; administering said complex to said mammal.
- 26. The method of claim 25, wherein said substance comprises DNA.
- 27. The method of claim 25, wherein said substance comprises a pharmaceutically active compound.
- 28. A method of delivering a substance to a hepatocyte in a mammal, said method comprising:
combining said substance with a mimetic as defined in claim 12 to yield an mimetic/substance complex; and administering said complex to said mammal.
- 29. The method of claim 28, wherein said substance comprises DNA.
- 30. The method of claim 28, wherein said substance comprises a pharmaceutically active compound.
- 31. An inhibitor for the binding of circumsporozoite polypeptide or a polypeptide as defined in claim 1 to a receptor of an hepatocyte from a malaria susceptible mammal, said inhibitor comprising a cleavage product of a heparan sulfate proteoglycan from the surface of said hepatocyte.
- 32. A method of inhibiting the binding of a circumsporozoite polypeptide to hepatocytes susceptible to sporozoite invasion, said method comprising:
supplying to the environment of said hepatocytes, the cleavage product of claim 31 in an amount effective to inhibit said binding, no later than exposure of said hepatocytes to said circumsporozoite protein.
- 33. The method of claim 32, wherein said circumsporozoite polypeptide is native circumsporozoite protein present on the surface of viable, infectious malarial sporozoites.
- 34. The method of claim 32 wherein said circumsporozoite polypeptide is selected from the group consisting of native circumsporozoite protein, recombinant circumsporozoite protein, and recombinant fragments of circumsporozoite protein each comprising Region II+.
- 35. The method of claim 32, wherein said hepatocytes are human hepatocytes.
- 36. An inhibitor for the binding of a circumsporozoite polypeptide or a polypeptide as defined in claim 1 to a receptor of an hepatocyte from a malaria susceptible mammal, said inhibitor comprising a mimetic of a cleavage product of a heparan sulfate proteoglycan from the surface of said hepatocyte.
- 37. A method of inhibiting the binding of a circumsporozoite polypeptide to hepatocytes susceptible to sporozoite invasion, said method comprising:
supplying to the environment of said hepatocytes, the peptide inhibitor of claim 36 in an amount effective to inhibit said binding, no later than exposure of said hepatocytes to said circumsporozoite protein.
- 38. The method of claim 37, wherein said circumsporozoite polypeptide is native circumsporozoite protein present on the surface of viable, infectious malarial sporozoites.
- 39. The method of claim 37, wherein said circumsporozoite polypeptide is selected from the group consisting of native circumsporozoite protein, recombinant circumsporozoite protein, and recombinant fragments of circumsporozoite protein each comprising Region II+.
- 40. The method of claim 37, wherein said hepatocytes are human hepatocytes.
- 41. A method of delivering a substance to a hepatocyte in a mammal, said method comprising:
combining said substance with an inhibitor as defined in claim 31 to yield an inhibitor/substance complex; and administering said complex to said mammal.
- 42. The method of claim 41, wherein said substance comprises DNA.
- 43. The method of claim 41, wherein said therapeutic agent comprises a pharmaceutically active agent.
- 44. A method of delivering a substance to a hepatocyte in a mammal, said method comprising:
combining said substance with an inhibitor as defined in claim 36 to yield an inhibitor/substance complex; and administering said complex to said mammal.
- 45. The method of claim 44, wherein said substance comprises DNA.
- 46. The method of claim 44, wherein said therapeutic agent comprises a pharmaceutically active agent.
Parent Case Info
[0001] This application is a continuation-in-part of U.S. Ser. No. 07/947,033, filed Sep. 17, 1992.
Government Interests
[0002] The United States Government has rights to this invention by virtue of the following grants: Grant No. 5T32GM07308 from the National Institutes of Health; NIH5T 32CA9161-16; and Grant No. DPE-0453-A-00-5012-00 from the Agency for International Development.
Continuations (1)
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Number |
Date |
Country |
Parent |
08119694 |
Sep 1993 |
US |
Child |
10098238 |
Mar 2002 |
US |
Continuation in Parts (1)
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Number |
Date |
Country |
Parent |
07947033 |
Sep 1992 |
US |
Child |
08119694 |
Sep 1993 |
US |