Claims
- 1. A process for the synthesis of a modified parathyroid hormone related polypeptide (PTHrP) of the formula:
- Ala Val Ser Glu Xaa.sup.5 Gln Leu Leu His Asp Xaa.sup.11 Gly Xaa.sup.13 Ser Ile Gln Asp Leu Xaa.sup.19 Arg Xaa.sup.21 Xaa.sup.22-31 Xaa.sup.32 Xaa.sup.33 Xaa.sup.34 Term, wherein:
- Xaa.sup.5 is His or Ala;
- Xaa.sup.11 and Xaa.sup.13 are independently Lys, Arg, or Leu;
- Xaa.sup.19 and Xaa.sup.21 are independently Ala or Arg;
- Xaa.sup.22-31 is selected from the group consisting of (SEQ ID NOS: 26, 27, 28, 29, and 30);
- Xaa.sup.32 is His or Lys;
- Xaa.sup.33 is Thr, Glu, or Ala;
- Xaa.sup.34 is Ala, hSer, Tyr, or Leu; and
- Term is OH, NR.sub.2, lactone, or Gly Arg Arg, where R is H or (C.sub.1 -C.sub.4) alkyl; and the pharmaceutically acceptable salts thereof, which process comprises expressing a nucleic acid sequence encoding said polypeptide.
- 2. A process of claim 1 wherein said polypeptide comprises a polypeptide wherein Xaa.sup.22-31 is (SEQ ID NO:26).
- 3. A process of claim 2 wherein said polypeptide is selected from the group consisting of (SEQ ID NOS: 7, 8 and 9).
- 4. A process of claim 1 wherein said polypeptide comprises a polypeptide wherein Xaa.sup.22-31 is (SEQ ID NO:27).
- 5. A process of claim 1 wherein said polypeptide comprises a polypeptide wherein Xaa.sup.22-31 is (SEQ ID NO:28).
- 6. A process of claim 1 wherein said polypeptide comprises a polypeptide wherein Xaa.sup.22-31 is (SEQ ID NO:29).
- 7. A process of claim 1 wherein said polypeptide comprises a polypeptide wherein Xaa.sup.22-31 is (SEQ ID NO:30).
- 8. A process for the synthesis of a modified parathyroid hormone (PTH) polypeptide of the formula:
- Xaa.sup.1 Val Ser Glu Ile Gln Xaa.sup.7 Xaa.sup.8 His Asn Leu Gly Lys His Leu Xaa.sup.16 Ser Xaa.sup.18 Xaa.sup.19 Arg Xaa.sup.21 Xaa.sup.22-31 His Ash Xaa.sup.34 Term, wherein:
- Xaa.sup.1 is Ser or Ala;
- Xaa.sup.7 is Leu or Phe;
- Xaa.sup.8 is Met or Nle;
- Xaa.sup.16 is Ash or Ser;
- Xaa.sup.18 is Leu, Met, or Nle;
- Xaa.sup.19 is Glu or Arg;
- Xaa.sup.21 is Val or Arg;
- Xaa.sup.22-31 is selected from (SEQ ID NOS: 26, 27, 28, 29, or 30);
- Xaa.sup.34 is Phe or Tyr; and Term is OH or NR.sub.2, where R is H or a (C.sub.1 -C.sub.4)alkyl; and the pharmaceutically acceptable salts thereof, which process comprises expressing a nucleic acid sequence encoding said polypeptide.
- 9. An expression vector comprising a nucleic acid sequence encoding a PTHrP analog of the formula:
- Ala Val Ser Glu Xaa.sup.5 Gln Leu Leu His Asp Xaa.sup.11 Gly Xaa.sup.13 Ser Ile Gln Asp Leu Xaa.sup.19 Arg Xaa.sup.21 Xaa.sup.22-31 Xaa.sup.32 Xaa.sup.33 Xaa.sup.34 Term, wherein:
- Xaa.sup.5 is His or Ala;
- Xaa.sup.11 and Xaa.sup.13 are independently Lys, Arg, or Leu;
- Xaa.sup.19 and Xaa.sup.21 are independently Ala or Arg;
- Xaa.sup.22-31 is selected from the group consisting of (SEQ ID NOS: 26, 27, 28, 29, and 30);
- Xaa.sup.32 is His or Lys;
- Xaa.sup.33 is Thr, Glu, or Ala;
- Xaa.sup.34 is Ala, hSer, Tyr, or Leu; and
- Term is OH, NR.sub.2, lactone, or Gly Arg Arg, where R is H or (C.sub.1 -C.sub.4) alkyl.
- 10. A host cell transformed with an expression vector of claim 9.
- 11. An expression vector encoding a modified parathyroid hormone (PTH) polypeptide of the formula:
- Xaa.sup.1 Val Ser Glu Ile Gln Xaa.sup.7 Xaa.sup.8 His Asn Leu Gly Lys His Leu Xaa.sup.16 Ser Xaa.sup.18 Xaa.sup.19 Arg Xaa.sup.21 Xaa.sup.22-31 His Asn Xaa.sup.34 Term, wherein:
- Xaa.sup.1 is Ser or Ala;
- Xaa.sup.7 is Leu or Phe;
- Xaa.sup.8 is Met or Nle;
- Xaa.sup.16 is Asn or Set;
- Xaa.sup.18 is Leu, Met, or Nle;
- Xaa.sup.19 is Glu or Arg;
- Xaa.sup.21 is Val or Arg;
- Xaa.sup.22-31 is selected from (SEQ ID NOS: 26, 27, 28, 29, or 30);
- Xaa.sup.34 is Phe or Tyr; and Term is OH or NR.sub.2, where R is H or a (C.sub.1 -C.sub.4)alkyl.
- 12. A host cell transformed with an expression vector of claim 11.
- 13. The polypeptide of SEQ ID NO: 26.
- 14. The polypeptide of SEQ ID NO: 27.
- 15. The polypeptide of SEQ ID NO: 28.
- 16. The polypeptide of SEQ ID NO: 29.
- 17. The polypeptide of SEQ ID NO: 30.
Parent Case Info
This is a division of application Ser. No. 07/915,247 filed Jul. 14, 1992, now U.S. Pat. No. 5,589,452.
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Divisions (1)
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Number |
Date |
Country |
Parent |
915247 |
Jul 1992 |
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