Claims
- 1. A composition comprising a compound represented by the formula (Tm-A-X-B)-Hn or (A-X-B-Tm)-Hn, wherein A is a protein synthesis inactivating toxin that is inactive until X is digested; X is a peptide susceptible to digestion by a viral protease; B is a lectin or a segment thereof, T is a targeting moiety, H is a hydrophobic agent, m is 0 or an integer of at least 1, and n is 0 or an integer of at least 1.
- 2. The composition of claim 1 wherein said viral protease is from a retrovirus, picornavirus, rhinovirus, hepatitis C virus, or herpesvirus.
- 3. The composition of claim 1 wherein A is a ricin A chain and B is a ricin B chain.
- 4. The composition of claim 1 wherein X is a member selected from the group. consisting of SEQ ID NO: 12 and SEQ ID NO: 13.
- 5. The composition of claim 1 wherein said targeting moiety is a member selected from the group consisting of antigen-binding proteins, viral surface components and segments thereof, proteins that bind viral surface components, growth factors, lectins, and carbohydrates.
- 6. The composition of claim 5 wherein said targeting moiety is a member selected from the group consisting of antibodies against gp120, antibodies against gp41, and the CD4 protein or segments thereof.
- 7. The composition of claim 5 wherein said targeting moiety is an antigen-binding protein that binds the CD4 glycoprotein.
- 8. The composition of claim 7 wherein the protein that binds the CD4 glycoprotein is gp120 or a segment thereof.
- 9. The composition of claim 1 wherein said targeting moiety is a GAG protein segment.
- 10. The composition of claim 1 wherein said hydrophobic agent is a member selected from the group consisting of bile acids, sterols, and saturated and unsaturated fatty acids.
- 11. The composition of claim 10 wherein said hydrophobic agent is a bile acid selected from the group consisting of cholic acid, deoxycholic acid, chenodeoxycholic acid, lithocholic acid, ursocholic acid, ursodeoxycholic acid, isoursodeoxycholic acid, lagodeoxycholic acid, glycocholic acid, taurocholic acid, glycodeoxycholic acid, glycochenodeoxycholic acid, dehydrocholic acid, hyocholic acid, hyodeoxycholic acid, and mixtures thereof.
- 12. The composition of claim 10 wherein said hydrophobic agent is a sterol selected from the group consisting of cholestanol, coprostanol, cholesterol, epicholesterol, ergosterol, ergocalciferol, and mixtures thereof.
- 13. The composition of claim 10 wherein said hydrophobic agent is a saturated or unsaturated fatty acid comprising about 4 to 20 carbon atoms.
- 14. The composition of claim 13 wherein said saturated or unsaturated fatty acid is a member selected from the group consisting of butyric acid, valeric acid, caproic acid, caprylic acid, capric acid, lauric acid, myristic acid, palmitic acid, stearic acid, oleic acid, linoleic acid, linolenic acid, eleostearic acid, and mixtures thereof.
- 15. The composition of claim 1 further comprising a pharmaceutically acceptable carrier admixed with the compound.
- 16. The composition of claim 1 wherein A, B, or both are from ADP-ribosyltransferases.
- 17. The composition of claim 1 wherein T comprises a myristylation signal sequence.
- 18. A composition comprising a compound represented by the formula N-X-A or A-X-N, wherein A is a protein synthesis inactivating toxin that is inactive until X is digested, X is a peptide susceptible to digestion by a viral protease, and N is an adenine moiety or functional equivalent thereof.
- 19. The composition of claim 18 wherein A is a ricin A chain.
- 20. The composition of claim 18 wherein X is a member selected from the group consisting of SEQ ID NO: 12 and SEQ ID NO: 13.
- 21. The composition of claim 18 wherein N is adenine.
- 22. The composition of claim 18 wherein N is a member selected from the group consisting of pteroic acid and 8-adeninethiol.
- 23. A method for treating a human immunodeficiency virus infection comprising administering an effective amount of a composition comprising:
(a) a member selected from the group consisting of:
(i) a compound represented by the formula (Tm-A-X-B)-Hn or (A-X-B-Tm)n, wherein A is a protein synthesis inactivating toxin that is inactive until X is digested; X is a peptide susceptible to digestion by a human immunodeficiency virus protease; B is a lectin or a segment thereof, T is a targeting moiety, H is a hydrophobic agent, m is 0 or an integer of at least 1, and n is 0 or an integer of at least 1, (ii) a compound represented by the formula N-X-A or A-X-N, wherein A is a protein synthesis inactivating protein that is inactive until X is digested, X is a peptide susceptible to digestion by a human immunodeficiency virus protease, and N is an adenine moiety or functional equivalent thereof, and (iii) mixtures of (i) and (ii); and ()) a pharmaceutically acceptable carrier.
- 24. The method of claim 23 wherein A is a ricin A chain and B is a ricin B chain.
- 25. The method of claim 23 wherein X is a member selected from the group consisting of SEQ ID NO: 12 and SEQ ID NO: 13.
- 26. The method of claim 23 wherein said targeting moiety is a member selected from the group consisting of antigen-binding proteins, viral surface components and segments thereof, proteins that bind viral surface components, growth factors, lectins, and carbohydrates.
- 27. The method of claim 26 wherein said targeting moiety is an antigen-binding protein that binds the CD4 glycoprotein.
- 28. The method of claim 27 wherein the protein that binds the CD4 glycoprotein is gp120 or a segment thereof.
- 29. The method of claim 23 wherein said targeting moiety is a GAG protein segment.
- 30. The method of claim 23 wherein said hydrophobic agent is a member selected from the group consisting of bile acids, sterols, and saturated and unsaturated fatty acids.
- 31. The method of claim 30 wherein said hydrophobic agent is a bile acid selected from the group consisting of cholic acid, deoxycholic acid, chenodeoxycholic acid, lithocholic acid, ursocholic acid, ursodeoxycholic acid, isoursodeoxycholic acid, lagodeoxycholic acid, glycocholic acid, taurocholic acid, glycodeoxycholic acid, glycochenodeoxycholic acid, dehydrocholic acid, hyocholic acid, hyodeoxycholic acid, and mixtures thereof.
- 32. The method of claim 30 wherein said hydrophobic agent is a sterol selected from the group consisting of cholestanol, coprostanol, cholesterol, epicholesterol, ergosterol, ergocalciferol, and mixtures thereof.
- 33. The method of claim 30 wherein said hydrophobic agent is a saturated or unsaturated fatty acid comprising about 4 to 20 carbon atoms.
- 34. The method of claim 33 wherein said saturated or unsaturated fatty acid is a member selected from the group consisting of butyric acid, valeric acid, caproic acid, caprylic acid, capric acid, lauric acid, myristic acid, palmitic acid, stearic acid, oleic acid, linoleic acid, linolenic acid, eleostearic acid, and mixtures thereof.
- 35. A nucleic acid encoding a peptide represented by the formula A-X-B wherein A is a protein synthesis inactivating toxin that is inactive until X is digested; X is a peptide susceptible to digestion by a human immunodeficiency virus protease; and B is a lectin or a segment thereof or other peptide targeting moiety.
- 36. The nucleic acid of claim 35 wherein A is a ricin A chain and B is a ricin B chain.
- 37. The nucleic acid of claim 35 wherein X is a member selected from the group consisting of SEQ ID NO: 12 and SEQ ID NO: 13.
- 38. A composition comprising a compound represented by the formula A-X-B, wherein A is a protein synthesis inactivating toxin that is inactive until X is digested; X is a peptide susceptible to digestion by a viral protease; and B is a lectin or a segment thereof.
- 39. The composition of claim 38 wherein said viral protease is from a retrovirus, picornavirus, rhinovirus, hepatitis C virus, or herpesvirus.
- 40. The composition of claim 38 wherein X is a member selected from the group consisting of SEQ ID NO: 12 and SEQ ID NO: 13.
- 41. The composition of claim 38 wherein A is a ricin A chain and B is a ricin B chain.
- 42. The composition of claim 38 wherein A is a ricin A chain and B is a fragment of a ricin B chain.
- 43. The composition of claim 38 further comprising a pharmaceutically acceptable carrier admixed with the compound.
- 44. A composition comprising a compound represented by the formula A-X-B, wherein A is a ricin A chain that is inactive until X is digested; X is a peptide susceptible to digestion by a viral protease and is a member selected from the group consisting of SEQ ID NO: 12 and SEQ ID NO: 13; and B is a ricin B chain or a segment thereof.
- 45. The composition of claim 44 further comprising a pharmaceutically acceptable carrier admixed with the compound.
RELATED APPLICATION
[0001] This application claims priority from U.S. provisional application Ser. No. 60/182,759 filed Feb. 16, 2000 and is incorporated by reference.
CONTRACTUAL ORIGIN OF THE INVENTION
[0002] This invention was made with United States Government support under Contract No. DE-AC07-94ID13223, now Contract No. DE-AC07-99ID13727 awarded by the United States Department of Energy. The United States Government has certain rights in the invention.
Provisional Applications (1)
|
Number |
Date |
Country |
|
60182759 |
Feb 2000 |
US |