Acetylene group-containing poly(alkylene oxide, oxyethylated polyol or olefinic alcohol)

• US 7,737,226 B2
• Filed: 01/24/2007
• Issued: 06/15/2010
• Est. Priority Date: 10/09/2003
• Status: Active Grant

• Current Assignee: Ambrx, Inc. (Johnson & Johnson)
• Original Assignee: Ambrx, Inc. (Johnson & Johnson)
• Inventors: Wilson, Troy E.
• Primary Examiner(s): SELLERS, ROBERT E
• Application Number:
  US11/657,143
• Publication Number:
  US 20070123693A1
• Time in Patent Office: 1,238 Days
• Field of Search: None
• US Class Current: 525/404
• CPC Class Codes: C08F 216/16 Monomers containing no hetero atoms other than the ether oxygen
• CPC Class Codes: C08F 8/02 Alkylation
• CPC Class Codes: C08F 8/30 Introducing nitrogen atoms or nitrogen-containing groups
• CPC Class Codes: C08G 65/325 containing nitrogen
• CPC Class Codes: C08G 65/329 with organic compounds
• CPC Class Codes: C08G 65/333 containing nitrogen

Abstract

The invention provides water-soluble compounds that include a polymer and at least one terminal azide or acetylene moiety. Also provided are highly efficient methods for the selective modification of proteins with PEG derivatives, which involves the selective incorporation of non-genetically encoded amino acids, e.g., those amino acids containing an azide or acetylene moiety, into proteins in response to a selector codon and the subsequent modification of those amino acids with a suitably reactive PEG derivative.

Claims

1. A water-soluble compound comprising a polymer having at least one terminal acetylene moiety, wherein said polymer is selected from the group consisting of poly(alkylene oxides), poly(oxyethylated polyols), and poly(olefinic alcohols), wherein said polymer has a molecular weight selected from the group consisting of between about 6,000 and about 80,000;

between about 6,000 and 20,000;

between about 80,000 and about 100,000;

about 6,000;

about 20,000;

about 80,000; and

about 100,000.

2. The water-soluble compound of claim 1 wherein said polymer is selected from the group consisting of poly(ethylene glycol), poly(propylene glycol), poly(oxyethylated glycerol), poly(oxyethylated sorbitol), poly(oxyethylated glucose), and poly(vinyl alcohol).

3. The water-soluble compound of claim 1 wherein said polymer is poly(ethylene glycol).

4. The water-soluble compound of claim 3 wherein said compound is poly(ethylene glycol)acetylene and said acetylene moiety is covalently attached directly to a polymer backbone.

5. The water-soluble compound of claim 1 wherein said polymer is a straight chain polymer that is not substituted beyond the acetylene moiety.

6. The water-soluble compound of claim 1 wherein said polymer is a random or block copolymer or terpolymer.

7. The water-soluble compound of claim 1 wherein said compound is stable in aqueous environments at a pH of about 11 or less.

8. A water soluble activated polymer that is stable against hydrolysis, said activated polymer having the formula:

R—

CH₂CH₂—

(OCH₂CH₂)_n—

C≡

CH

wherein n is from about 5 to 3,000, and R is a capping group, a functional group, or a leaving group that can be the same or different from the acetylene.

9. The water soluble activated polymer of claim 8 wherein R is selected from the group consisting of hydroxyl, protected hydroxyl, alkoxyl, N-hydroxysuccinimidyl ester, 1-benzotriazolyl ester, N-hydroxysuccinimidyl carbonate, 1-benzotriazolyl carbonate, acetal, aldehyde, aldehyde hydrates, alkenyl, acrylate, methacrylate, acrylamide, active sulfone, amine, aminooxy, protected amine, hydrazide, protected hydrazide, protected thiol, carboxylic acid, protected carboxylic acid, isocyanate, isothiocyanate, maleimide, vinylsulfone, dithiopyridine, vinylpyridine, iodoacetamide, epoxide, glyoxals, diones, mesylates, tosylates, tresylate, alkene, and ketone.

10. The water soluble activated polymer of claim 8 wherein n is from about 5 to 2,200.

11. The water soluble activated polymer of claim 8 wherein n is from about 34 to 1,100.

12. The water soluble activated polymer of claim 8 wherein n is from about 45 to 110.

13. The water soluble activated polymer of claim 8 wherein R is methoxy (CH₃O—

).

14. The water soluble activated polymer of claim 8 wherein R is carboxylic acid (HO₂C—

).

15. The water soluble activated polymer of claim 8 wherein R is amine(H₂N—

).

16. The water soluble activated polymer of claim 8 wherein R is maleimide.

17. The water soluble activated polymer of claim 8 wherein R is reactive with amines.

18. The water soluble activated polymer of claim 8 wherein R is reactive wit electrophilic carbonyl groups.

19. The water soluble activated polymer of claim 8 wherein R is reactive with thiols.

20. The water soluble activated polymer of claim 8 wherein R is reactive with hydroxyls.