Modified Beta Thymosin Peptides

• US 20080248993A1
• Filed: 01/17/2006
• Published: 10/09/2008
• Est. Priority Date: 01/14/2005
• Status: Abandoned Application

• Current Assignee: Friedrich-Alexander-Universitat Erlangen-Nurnberg, RegeneRx Biopharmaceuticals, Inc.
• Original Assignee: RegeneRx Biopharmaceuticals, Inc., Universitat Erlangen-Nurnberg
• Inventors: Goldstein, Allan L., Crockford, David, Huff, Thomas, Hannappel, Ewald
• Application Number:
  US11/722,979
• Publication Number:
  US 20080248993A1
• Time in Patent Office: Days
• US Class Current: 514/2
• CPC Class Codes: A61K 38/00 Medicinal preparations containing peptides peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00
• CPC Class Codes: C07K 14/57581 Thymosin; Related peptides

Abstract

A composition including an oxidized or superoxidized methionine-containing beta thymosin peptide, isoform thereof, fragment thereof, isolated R-enantiomer thereof or isolated S-enantiomer thereof, other than racemic thymosin beta 4 sulfoxide, or a modified beta thymosin peptide, isoform or fragment thereof with an amino acid substituent substituted for at least one methionine of an amino acid sequence of a normally methionine-containing beta thymosin peptide, isoform or fragment thereof, and method for forming same.

Claims

1. A composition comprising an oxidized or superoxidized modified normally methionine-containing beta thymosin peptide, isoform thereof, fragment thereof, isolated R-enantiomer thereof or isolated S-enantiomer thereof, other than racemic thymosin beta 4 sulfoxide, or comprising a modified beta thymosin peptide, isoform or fragment thereof having a non-methionine amino acid substituent substituted for at least one methionine of an amino acid sequence of a normally methionine-containing beta thymosin peptide, isoform or fragment thereof.

2. The composition of claim 1 wherein said normally methionine-containing beta thymosin peptide is Tβ

4, Tβ

4^ala, Tβ

4^xen, Tβ

9^met, Tβ

10 or Tβ

13.

3. The composition of claim 1 wherein said amino acid substituent is leucine, valine, isoleucine, alanine, phenylalanine or proline.

4. The composition of claim 1 wherein said methionine-containing beta thymosin peptide is Tβ

4.

5. The composition of claim 1 wherein said amino acid substituent is leucine, valine, isoleucine, alanine, phenylalanine or proline.

6. The composition of claim 1 wherein said amino acid substituent is at least one of neutral, non-polar, hydrophobic or non-oxidizing.

7. The composition of claim 1 wherein said amino acid substituent inhibits oxidation of said peptide.

8. The composition of claim 1 comprising a modified beta thymosin peptide, isoform or fragment thereof having a non-methionine amino acid substituent other than leucine substituted for at least one methionine of an amino acid sequence of a methionine-containing beta thymosin peptide other than Tβ

4, or an isoform or fragment of a normally methionine-containing beta thymosin peptide.

9. The composition of claim 1 comprising peptide Tβ

4^leu, which comprises a modified Tβ

4 amino acid sequence having leucine substituted for methionine at position 6 thereof.

10. The composition of claim 1 wherein the modified methionine-containing beta thymosin peptide, isoform or fragment thereof is a sulfoxide.

11. The composition of claim 1 wherein the modified methionine-containing beta thymosin peptide, isoform or fragment thereof is a sulfone.

12. The composition of claim 1 comprising thymosin beta 4 sulfone.

13. The composition of claim 1 comprising Tβ

4^ala sulfone, Tβ

4^xen sulfone, Tβ

4^met sulfone, Tβ

10 sulfone or Tβ

13 sulfone.

14. The composition of claim 1 comprising an isolated R-enantiomer.

15. The composition of claim 1 comprising an isolated S-enantiomer.

16. The composition of claim 1 comprising an isolated R-enantiomer of thymosin beta 4 sulfoxide.

17. The composition of claim 1 comprising an isolated S-enantiomer of thymosin beta 4 sulfoxide.

18. A method for forming a beta thymosin sulfone peptide according to claim 1, comprising contacting a normally methionine-containing beta thymosin peptide with an acid, so as to form a beta thymosin sulfone peptide.

19. The method of claim 18 wherein said acid comprises at least one of performic acid or peracetic acid.

20. A method of forming a composition according to claim 1, comprising an isolated R-beta thymosin sulfoxide or sulfone, the method comprising separating an R-beta thymosin sulfoxide or sulfone from a mixture of corresponding R-beta thymosin sulfoxide or sulfone and S-beta thymosin sulfoxide or sulfone.

21. A method of forming a composition according to claim 1, comprising an isolated S-beta thymosin sulfoxide or sulfone, the method comprising separating an S-beta thymosin sulfoxide or sulfone from a mixture containing corresponding S-beta thymosin sulfoxide or sulfone and R-beta thymosin sulfoxide or sulfone.

22. A method for forming a modified beta thymosin peptide, isoform or fragment thereof as defined in claim 1, comprising substituting a non-methionine amino acid substituent for at least one methionine of amino acid sequence of a normally methionine-containing beta thymosin peptide, isoform or fragment thereof, so as to form a modified beta thymosin peptide, isoform or fragment thereof.

23. The method of claim 22 wherein said amino acid substituent is leucine, valine, isoleucine, alanine, phenylalanine or proline.

24. The method of claim 22 for forming peptide Tβ

4^leu, comprising substituting amino acid leucine for methionine at position 6 of Tβ

4 so as to form peptide Tβ

4^leu.