Claims
- 1. A synthetic protein containing a pseudo-amino acid residue whose side chain has the formula: —S—Raa, where Raa is an optionally substituted terminal portion of a ribosomally-specified amino acid side chain, or an analog of said terminal portion of a ribosomally-specified amino acid side chain.
- 2. The synthetic protein of claim 1, wherein said side chain —S—Raa has the same chain length as the side chain of said ribosomally-specified amino acid.
- 3. The synthetic protein of claim 1, wherein said side chain —S—Raa has a greater chain length than the side chain of said ribosomally-specified amino acid.
- 4. The synthetic protein of claim 1, wherein said protein has a biological activity possessed by a ribosomally-specified bioactive protein.
- 5. The synthetic protein of claim 4, wherein said side chain —S—Raa of said pseudo amino acid residue mimics the structure or function of a ribosomally-specified amino acid at a corresponding position in said bioactive protein.
- 6. The synthetic protein of claim 4, wherein said side chain —S—Raa of said pseudo amino acid residue alters the structure or function of a ribosomally-specified amino acid at a corresponding position in said bioactive protein.
- 7. The synthetic protein of claim 4, wherein said synthetic protein has a monomer molecular weight greater than about 25 kDa.
- 8. The synthetic protein of claim 4, wherein said ribosomally produced bioactive protein contains a cysteine residue.
- 9. The synthetic protein of claim 8, wherein said pseudo amino acid residue is at a position other than one corresponding to the position of said cysteine residue in said ribosomally produced bioactive protein.
- 10. The synthetic protein of claim 1, wherein a plurality of amino acid residues of said protein are bound to adjacent amino acid residues by an amide bond.
- 11. The synthetic protein of claim 10, wherein each amino acid residue is bonded to its adjacent amino acid residues by amide bonds.
- 12. The synthetic protein of claim 1, wherein said protein is composed of a plurality of amino acid residues wherein at least one of such amino acid residues is bonded to an adjacent amino acid residue by a non-amide bond.
- 13. The synthetic protein of claim 12, wherein said non-amide bond is selected from the group consisting of a thioester bond, a thioether bond, and an oxime bond.
- 14. The synthetic protein of claim 1, wherein said pseudo-amino acid residue is a D-configuration amino acid residue.
- 15. The synthetic protein of claim 1, wherein said pseudo-amino acid residue is an L-configuration amino acid residue.
- 16. The synthetic protein of claim 1, wherein said pseudo-amino acid residue is selected from the group consisting of a pseudo-arginine; a pseudo-asparagine; a pseudo-aspartate; a pseudo-dopamine; a pseudo-glutamate; a pseudo-glutamine; a pseudo-histidine; a pseudo-isoleucine; a pseudo-leucine; a pseudo-lysine; a pseudo-methionine; a pseudo-phenyalanine; a pseudo-serine; a pseudo-threonine; a pseudo-tryptophan; a pseudo-tyrosine; and a pseudo-valine.
- 17. The synthetic protein of claim 16 wherein said pseudo-amino acid residue is a pseudo-glutamate.
- 18. The synthetic protein of claim 4, wherein said ribosomally produced bioactive protein is a mammalian protein.
- 19. The synthetic protein of claim 18, wherein said mammalian protein is selected from the group consisting of a human, simian, bovine, murine, porcine, ovine, and equine protein.
- 20. The synthetic protein of claim 18, wherein said mammalian protein is a human protein.
- 21. The synthetic protein of any of claims 19-20, wherein said protein has a bioactivity selected of a protein receptor or fragment thereof, of a protein receptor ligand or fragment thereof, or of a cytokine.
- 22. The synthetic protein of claim 21, wherein said synthetic bioactive protein has a bioactivity of a cytokine.
- 23. The synthetic protein of claim 22, wherein said cytokine is selected from the group consisting of an interleukin, a lymphokine, a RANTES protein, an erythropoiesis stimulating protein, tumor necrosis factor (TNF), an interferon, a growth factors and a single peptide hormone.
- 24. The synthetic protein of claim 23, wherein said cytokine is an erythropoiesis stimulating protein.
- 25. The synthetic protein of claim 24, wherein said erythropoiesis stimulating protein is erythropoietin.
- 26. The synthetic protein of claim 25, wherein said synthetic bioactive protein is selected from the group consisting of SEP-0, SEP-1, and SEP-3.
- 27. The synthetic protein of claim 22, wherein said cytokine is a RANTES protein.
- 28. The synthetic protein of claim 22, wherein said cytokine is a growth factor.
- 29. The synthetic protein of claim 28, wherein said growth factor is G-CSF.
- 30. The synthetic protein of claim 1, wherein said synthetic protein comprises one or more amino acid residues that are modified by one or more polymer adducts.
- 31. The synthetic protein of claim 4, wherein said ribosomally produced bioactive protein is glycosylated at one or more glycosylation sites.
- 32. The synthetic protein of claim 31, wherein said synthetic protein comprises one or more amino acid residues that are modified by one or more polymer adducts at amino acid residue(s) that correspond to at least one of said glycosylation sites of said ribosomally produced bioactive protein.
- 33. A molecularly homogeneous pharmaceutical composition comprising a synthetic protein, wherein said protein possesses a biological activity that mimics a biological activity associated with a ribosomally-specified bioactive mammalian protein, and has a monomer molecular weight greater than about 25 kDa, and contains a pseudo-amino acid residue whose side chain has the formula: —S—Raa, where Raa is selected from the group consisting of an optionally substituted terminal portion of a ribosomally-specified amino acid side chain, or an analog thereof.
- 34. The pharmaceutical composition of claim 33, wherein said composition comprises a mixture of at least two of said molecularly homogeneous pharmaceutical compositions.
- 35. The pharmaceutical composition of claim 33, wherein said ribosomally-specified bioactive mammalian protein is selected from the group consisting of a human, simian, bovine, murine, porcine, ovine, and equine protein.
- 36. The pharmaceutical composition of claim 33, wherein said ribosomally-specified bioactive mammalian protein is a human protein.
- 37. The pharmaceutical composition of claim 36, wherein said synthetic protein has a biological activity of a protein receptor or fragment thereof, of a protein receptor ligand or fragment thereof, or of a cytokine.
- 38. The pharmaceutical composition of claim 37, wherein said synthetic protein has a biological activity of a cytokine.
- 39. The pharmaceutical composition of claim 38, wherein said cytokine is selected from the group consisting of an interleukin, a RANTES protein, a lymphokine, an erythropoiesis stimulating protein, tumor necrosis factor (TNF), an interferon, a growth factor and a single peptide hormone.
- 40. The pharmaceutical composition of claim 39, wherein said cytokine is an erythropoiesis stimulating protein.
- 41. The pharmaceutical composition of claim 40, wherein said erythropoiesis stimulating protein is erythropoietin.
- 42. The pharmaceutical composition of claim 41, wherein said synthetic protein is selected from the group consisting of SEP-0, SEP-1, and SEP-3.
- 43. The pharmaceutical composition of claim 38, wherein said cytokine is a RANTES protein.
- 44. The pharmaceutical composition of claim 39, wherein said cytokine is a growth factor.
- 45. The pharmaceutical composition of claim 44, wherein said growth factor is G-CSF.
- 46. A method of treating a human disease or condition that comprises administering to an individual in need of such treatment an effective amount of a pharmaceutical composition comprising one or more molecularly homogeneous pharmaceutical compositions each comprising a synthetic protein, wherein said synthetic protein has a monomer molecular weight greater than about 25 kDa, and contains a pseudo-amino acid residue whose side chain has the formula: —S—Raa, where Raa is selected from the group consisting of an optionally substituted terminal portion of a ribosomally-specified amino acid side chain, or an analog thereof; said synthetic protein possessing a biological activity that mimics a biological activity of a ribosomally-specified bioactive human protein receptor or fragment thereof, protein receptor ligand or fragment thereof, or a cytokine.
- 47. The method of claim 46, wherein said synthetic protein has a biological activity of a cytokine.
- 48. The method of claim 47, wherein said cytokine is selected from the group consisting of an interleukin, a lymphokine, a RANTES protein, an erythropoiesis stimulating protein, tumor necrosis factor (TNF), an interferon, a growth factor and a single peptide hormone.
- 49. The method of claim 48, wherein said cytokine is an erythropoiesis stimulating protein.
- 50. The method of claim 49, wherein said erythropoiesis stimulating protein is erythropoietin.
- 51. The method of claim 50, wherein said synthetic bioactive protein is selected from the group consisting of SEP-0, SEP-1, and SEP-3.
- 52. The method of claim 48, wherein said cytokine is a RANTES protein.
- 53. The method of claim 48, wherein said cytokine is a growth factor.
- 54. The method of claim 53, wherein said growth factor is G-CSF.
- 55. A method for synthesizing a desired polypeptide of formula:
- 56. The method of claim 55, wherein X is a halogen.
- 57. The method of claim 56, wherein said halogen is F, I or Br.
- 58. The method of claim 55, wherein said amino acid residue aay is selected from the group consisting of a pseudo-arginine; a pseudo-asparagine; a pseudo-aspartate; a pseudo-dopamine; a pseudo-glutamate; a pseudo-glutamine; a pseudo-histidine; a pseudo-isoleucine; a pseudo-leucine; a pseudo-lysine; a pseudo-methionine; a pseudo-phenyalanine; a pseudo-serine; a pseudo-threonine; a pseudo-tryptophan; a pseudo-tyrosine; and a pseudo-valine.
- 59. A polypeptide of formula:
- 60. The polypeptide of claim 59, wherein X is a halogen.
- 61. The polypeptide of claim 60, wherein said halogen is F, I or Br.
- 62. The polypeptide of claim 59, wherein said amino acid residue aay is selected from the group consisting of a pseudo-arginine; a pseudo-asparagine; a pseudo-aspartate; a pseudo-dopamine; a pseudo-glutamate; a pseudo-glutamine; a pseudo-histidine; a pseudo-isoleucine; a pseudo-leucine; a pseudo-lysine; a pseudo-methionine; a pseudo-phenyalanine; a pseudo-serine; a pseudo-threonine; a pseudo-tryptophan; a pseudo-tyrosine; and a pseudo-valine.
CROSS-REFERENCE TO RELATED APPLICATIONS
[0001] This application is a continuation-in-part of U.S. Patent Applications Serial. Nos. 60/231,339 (filed Sep. 8, 2000) and 60/236,377 (filed Sep. 29, 2000), both of which applications are herein incorporated by reference in their entirety.
PCT Information
Filing Document |
Filing Date |
Country |
Kind |
PCT/US01/21935 |
7/12/2001 |
WO |
|