Galactosyl nucleotide sugars

• US 7,439,043 B2
• Filed: 04/09/2003
• Issued: 10/21/2008
• Est. Priority Date: 10/10/2001
• Status: Expired due to Fees

• Current Assignee: Novo Nordisk A/S
• Original Assignee: Neose Technologies, Inc.
• Inventors: DeFrees, Shawn, Bayer, Robert, Chen, Xi, Hakes, David, Bowe, Caryn, Zopf, David
• Primary Examiner(s): Tsang; Cecilia
• Assistant Examiner(s): HEARD, THOMAS SWEENEY
• Application Number:
  US10/411,043
• Publication Number:
  US 20080206808A1
• Time in Patent Office: 2,022 Days
• Field of Search: None
• US Class Current: 435/89
• CPC Class Codes: C07H 19/00 Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof
• CPC Class Codes: C12P 21/02 having a known sequence of two or more amino acids, e.g. glutathione

Abstract

The invention includes methods and compositions for remodeling a peptide molecule, including the addition or deletion of one or more glycosyl groups to a peptide, and/or the addition of a modifying group to a peptide.

Claims

1. A modified galactosyl nucleotide having a formula selected from:

2. The modified galactosyl nucleotide according to claim 1 wherein each of said poly(alkylene oxide) moiety is a member independently selected from linear or branched poly(ethylene glycol) and linear or branched poly(propylene glycol).

3. The modified galactosyl nucleotide according to claim 2 wherein said poly(ethylene glycol) is monomethoxy-poly(ethylene glycol).

12. The modified galactosyl nucleotide according to claim 2, wherein said poly(ethylene glycol) has a molecular weight that is essentially homodisperse.

16. The modified galactosyl nucleotide according to claim 1, wherein

X is O;

R₁ is H;

Y is O;

R₃ is H;

Z is O;

R₂ is H;

A is NH; and

R₄ is a linker to a water-soluble polymer.

17. The modified galactosyl nucleotide according to claim 1, wherein the cation is a member selected from sodium, potassium, lithium, magnesium, manganese and zinc.

20. The modified galactosyl nucleotide according to claim 1, wherein said modified galactosyl nucleotide has a formula, which is a member selected from:

21. The modified galactosyl nucleotide according to claim 20, wherein R is H.

22. The modified galactosyl nucleotide according to claim 20, wherein R¹ and R⁴ are a linker to said poly(alkylene oxide) moiety.

23. The modified galactosyl nucleotide according to claim 1, wherein said modified galactosyl nucleotide is a substrate for a glycosyltransferase.

24. The modified galactosyl nucleotide according to claim 23, wherein said glycosyltransferase is a member selected from galactosyltransferase and GalNAc transferase.

4. A poly(ethylene glycol) molecule having the formula:

5. The poly(ethylene glycol) molecule according to claim 4 wherein

R is a member selected from H, alkyl, and aryl;

X, Y and W are O;

Z is (CH₂)_pU(CH₂)_sC(Y′

)V

wherein

U is NH; and

Y′

is O.

13. The poly(ethylene glycol) molecule according to claim 4, wherein said poly(ethylene glycol) has a molecular weight that is essentially homodisperse.

14. The poly(ethylene glycol) molecule according to claim 4, wherein said poly(ethylene glycol) is monomethoxy-poly(ethylene glycol).

18. The poly(ethylene glycol) molecule according to claim 4, wherein

Z is (CH₂)_pU(CH₂)_s[C(Y′

)]_rV;

p is 0;

s is 0;

U is NH and r is a member selected from 0 and 1.

25. The poly(ethylene glycol) molecule according to claim 4, wherein said peptide is a therapeutic peptide.

6. A poly(ethylene glycol) molecule having the formula:

7. The poly(ethylene glycol) molecule according to claim 6, where said sugar nucleotide is a member selected from UDP-glycoside, CMP-glycoside, and GDP-glycoside.

8. The poly(ethylene glycol) molecule according to claim 7, wherein said sugar nucleotide is a member selected from UDP-galactose, UDP-galactosamine, UDP-glucose, UDP-glucosamine, GDP-mannose, GDP-fucose, CMP-sialic acid, and CMP-NeuAc.

15. The poly(ethylene glycol) molecule according to claim 6, wherein said poly(ethylene glycol) has a molecular weight that is essentially homodisperse.

19. The poly(ethylene glycol) molecule according to claim 6, wherein

Z is (CH₂)_sU(CH₂)_v[C(Y′

)]_rV;

s is 0;

v is 0;

U is NH and r is a member selected from 0 and 1.

26. The poly(ethylene glycol) molecule according to claim 6, wherein said peptide is a therapeutic peptide.

9. A modified galactosyl nucleotide comprising a poly(ethylene glycol) moiety covalently joined to a sugar moiety of uridine-5′

-diphosphate galactose.

10. The modified galactosyl nucleotide according to claim 9 wherein said poly(ethylene glycol) moiety is a member selected from linear and branched poly(ethylene glycol).

11. The modified galactosyl nucleotide according to claim 9 wherein said poly(ethylene glycol) moiety is monomethoxy-poly(ethylene glycol).

27. A modified galactosyl nucleotide having a formula selected from: