Poly(ethylene or propylene glycol)-containing polymer

• US 5,352,756 A
• Filed: 06/11/1993
• Issued: 10/04/1994
• Est. Priority Date: 02/13/1992
• Status: Expired due to Term

• Current Assignee: Novo Nordisk A/S
• Original Assignee: Carlsberg A/S
• Inventors: Meldal, Morten P.
• Primary Examiner(s): Kight, III, John
• Assistant Examiner(s): BOYKIN, TERRESSA M
• Application Number:
  US08/075,758
• Time in Patent Office: 480 Days
• Field of Search: 525/50, 525/539, 528/296, 528/304, 528/312, 528/320
• US Class Current: 525/50
• CPC Class Codes: C07H 21/00 Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids
• CPC Class Codes: C07K 1/042 characterised by the nature of the carrier
• CPC Class Codes: C08F 290/062 Polyethers

Abstract

A crosslinked poly(ethylene or propylene)glycol-containing polymer which has a unique spatial structure and can be designed especially for application as a chromatographic resin or as a solid support for the synthesis of peptides, oligonucleotides or oligosaccharides or as a substrate for the immobilization of proteins. The polymer is formed by radical copolymerization of derivatized poly(ethylene or propylene) glycol bis-end substituted with a moiety selected from the group consisting of acryloylalkyl, acryloylaryl, acrylamidoalkyl and acrylamidoaryl with an acrylic amide, nitrile or ester. When it is to be used as a solid support or immobilization substrate, the polymer will incorporate a spacer comprising functional groups for the attachment of peptides, proteins, nucleotides or saccharides such as those selected from the group consisting of amino, alkylamino, hydroxy, carboxyl, mercapto, sulfeno, sulfino, sulfo and derivatives thereof.

Claims

1. A crosslinked poly(ethylene or propylene) glycol-containing polymer formed by radical copolymerization of a derivatived poly(ethylene or propylene) glycol of the formula ##STR6## wherein a) n is an integer of from 4 to 2,000,

b) R" is H or CH₃,

c) R is --(CR'"'"'₂)_s --(C₆ R'"'"'₆)_t --(CR'"'"'₂)_u -- wherein

each R'"'"' is H, alkyl, aralkyl, substituted aralkyl, aryl or substituted aryl, said substituted aralkyl and substituted aryl being ring substituted with alkyl, hydroxy, mercapto, nitro, amino, mono- or dialkylamino, or halogen;

d) q is zero or 1 and s, t and u each is zero or an integer of 1-10, provided that the polymer contains no ester bonds, with an acrylic compound of the formula ##STR7## wherein R¹ is --CY--X--R⁵ or --CN, and R², R³ and R⁴ each is H, alkyl, aralkyl, aryl, --CY--X--R⁵ or --CN, where Y is O or S, X is O, S or NR⁶, R⁵ is alkyl, aralkyl or aryl, and R⁶ is H or H⁵.

2. A polymer according to claim 1, wherein the copolymerization has further included a spacer molecule comprising functional groups for the attachment of peptides, proteins, nucleotides or saccharides.

3. A polymer according to claim 2 which incorporates a spacer comprising functional groups selected from the group consisting of amino, alkylamino, hydroxy, carboxyl, mercapto, sulfeno, sulfino, sulfo and derivatives thereof.

4. A polymer according to claim 2 which is formed by copolymerization of a derivatized poly(ethylene or propylene) glycol of the formula I, wherein n, q, R" and R are as defined in claim 1 with an acrylamide of the formula ##STR8## and with a spacer molecular of the formula ##STR9## wherein n, q, R" and R are as defined for formula I in claim 1.

5. A polymer according to claim 4 which is composed of 60% of 0,0'"'"'-bis-(2-acrylamidoprop-1-yl)-PEG₁₉₀₀ (1), 20% of 0-(2-acrylamidoprop-1-yl)-0 '"'"'-(2-aminoprop-1-yl)-PPG₃₀₀ (2) and 20% of N,N-dimethyl acrylamide (3).

6. A polymer according to claim 4 derivatized with any of the linkers normally used in peptide synthesis.

7. A polymer according to claim 6 said linker being 4-[fluorenylmethyloxycarbamido(2,4-dimethoxyphenyl)methyl]phenoxyacetic acid of the formula ##STR10## 4-hydroxymethylphenoxyacetic acid, 4-hydroxymethylbenzamide or 4-hydroxymethyl-3-nitrobenzamide.

8. A solid support for continuous flow or batchwise synthesis of peptides said support comprising a polymer according to claim 1.

9. A solid support for continuous flow or batchwise synthesis of oligonucleotides said support comprising a polymer according to claim 1.

10. A solid support for the synthesis of oligosaccharides said support comprising a polymer according to claim 1.

11. A solid support according to claim 1 said support being suitable for synthesis by enzymatic reactions.

12. A solid support according to claim 10 for enzymatic synthesis of oligosaccharides with glycosyltransferases.

13. A solid support for the immobilization of proteins said support comprising a polymer according to claim 1.

14. A resin for application in chromatographic separations said resin comprising a polymer according to claim 1.

15. A method of continuous flow or batchwise synthesis of a peptide wherein the peptide during the synthesis is attached to a solid support comprising a polymer according to claim 1 and at the end of the synthesis is cleaved from said solid support.

16. A method of continuous flow or batchwise synthesis of an oligonucleotide wherein the oligonucleotide during the synthesis is attached to a solid support comprising a polymer according to claim 1 and at the end of the synthesis is cleaved from said solid support.

17. A method of continuous flow or batchwise synthesis of an oligosaccharide wherein the oligosaccharide during the synthesis is attached to a solid support comprising a polymer according to claim 1 and at the end of the synthesis is cleaved from said solid support.

18. A method according to claim 1 wherein the synthesis involves an enzymatic reaction.

19. A method according to claim 17 for enzymatic synthesis of an oligosaccharide with a glycosyltransferase.

20. A method of immobilizing a protein wherein the protein is attached to a solid support comprising a polymer according to claim 1.

21. A method of performing chromatographic separations which comprises the use of a chromatographic resin comprising a polymer according to claim 1.