Active carbonates of polyalkylene oxides for modification of polypeptides

• US 5,122,614 A
• Filed: 04/19/1990
• Issued: 06/16/1992
• Est. Priority Date: 04/19/1989
• Status: Expired due to Term

• Current Assignee: Enzon Pharmaceuticals Inc. (Icahn Associates Holding LLC)
• Original Assignee: Enzon Pharmaceuticals Inc. (Icahn Associates Holding LLC)
• Inventors: Zalipsky, Shmuel
• Primary Examiner(s): Raymond, Richard L.
• Application Number:
  US07/511,243
• Time in Patent Office: 789 Days
• Field of Search: 546/208, 546/243, 548/435, 548/465, 548/479, 548/520, 548/542, 548/340, 548/928, 430/406, 430/410, 430/389, 430/363, 435/177, 435/188
• US Class Current: 548/520
• CPC Class Codes: A61K 47/60 the organic macromolecular compound being a polyoxyalkylene oligomer, polymer or dendrimer, e.g. PEG, PPG, PEO or polyglycerol
• CPC Class Codes: C07D 207/46 with hetero atoms directly attached to the ring nitrogen atom

Abstract

Poly(ethylene glycol)-N-succinimide carbonate and its preparation are disclosed. Polyethylene glycol (PEG) is converted into its N-succinimide carbonate derivative. This form of the polymer reacts readily with amino groups of proteins in aqueous buffers. The modified proteins have PEG-chains grafted onto the polypeptide backbone by means of stable, hydrolysis-resistant urethane (carbamate) linkages.

Claims

1. A compound having the structure:

##STR8## wherein R₁ is H--, H₃ C--, or an oxycarbonyl-N-dicarboximide group;

wherein each R₂, R₃, and R₄ is an alkyl group which may be straight or branched, and wherein each R₂, R₃, and R₄ may be independently the same as, or different from, the others of R₂, R₃, and R₄ ;

wherein R₅ is an N-dicarboximide group; and

wherein a is an integer between 1 and 1000 and each of b and c is an integer between 0 and 1000, and the sum of a, b, and c is between 10 and 1000.

2. A compound of claim 1, wherein each of R₂, R₃, R₄ is CH₂ CH₂, CH₂ CHCH₃, or CH₂ CH₂ CH₂ CH₂.

3. A compound according to claim 1 wherein each of R₁ and R₂ is an N-dicarboximide group selected from the group consisting of N-succinimide, N-phthalimide, N-glutarimide, N-tetrahydrophthalimide and N-norbornene-2,3-dicarboximide and where R₁ and R₅ may be the same or different.

4. A compound according to claim 3 wherein R₅ is an N-succinimide group.

5. A compound of claim 1 having the structure:

##STR9## where R₁ is H₃ C--, or H--; and

a is an integer between 10 and 1000.

6. A compound of claim 1 having the structure ##STR10## wherein a is an integer between 10 and 1000.