Synthetic amino acid-and/or peptide-containing graft copolymers

• US 4,908,404 A
• Filed: 08/22/1988
• Issued: 03/13/1990
• Est. Priority Date: 08/22/1988
• Status: Expired due to Term

• Current Assignee: AL Marzook United Commercial Co.
• Original Assignee: BiopolyMed, Inc.
• Inventors: Chaturvedi, Nishith, Benedict, Christine V.
• Primary Examiner(s): Kight, John
• Assistant Examiner(s): Nutter, Nathan M.
• Application Number:
  US07/234,896
• Time in Patent Office: 568 Days
• Field of Search: 525/54.1, 525/54.11, 527/200, 527/207
• US Class Current: 525/54.11
• CPC Class Codes: C08F 8/30 Introducing nitrogen atoms or nitrogen-containing groups

Abstract

A water soluble cationic peptide-containing graft copolymer exhibiting a number average molecular weight of from about 30,000 to about 500,000 are provided comprising:

(a) a polymeric backbone containing or capable of modification to include free primary or secondary amine functional groups for reaction with an amino acid or peptide graft and exhibiting a number average molecular weight from about 10,000 to about 250,000; and

(b) an amino acid or peptide graft reacted with from at least about 5% to about 100% of the primary or secondary amine functional groups of the polymeric backbone, wherein said amino acid or peptide graft comprises at least one 3,4-dihydroxyphenylalaine (Dopa) amino acid or a precursor thereof capable of hydroxylation to the Dopa form.

The peptide-containing graft copolymers of the present invention can vary in (a) molecular weight, cationicity, percent substitution of the amino acid or peptide unit grafted to the polymer backbone and (b) the chemical and physical structure of the peptide-containing graft copolymer itself, thereby enabling specific tailoring of the polymers of the present invention for particular end-use applications.

Claims

1. A water-soluble cationic peptide-containing graft copolymer exhibiting a number average molecular weight of from about 30,000 to about 500,000 comprising:

(a) a polymeric backbone containing or capable of modification to include free primary or secondary amine functional groups for reaction with an amino acid or peptide graft, said polymeric backbone exhibiting a number average molecular weight of from about 10,000 to about 250,000; and

(b) an amino acid or peptide graft reacted with from at least 5% to about 100% of said primary or secondary amine functional groups of said polymeric backbone, wherein said amino acid or peptide graft comprises at least one 3,4-dihydroxyphenylalanine (Dopa) amino acid or a precursor thereof capable of hydroxylation to the Dopa form.

2. A peptide-containing graft copolymer according to claim 1 wherein the number average molecular weight of said copolymer ranges from about 50,000 to about 350,000.

3. A peptide-containing graft copolymer according to claim 1 wherein the number average molecular weight of said copolymer ranges from about 70,000 to about 350,000.

4. A peptide-containing graft copolymer according to claim 1 wherein the number average molecular weight of said copolymer is about 100,000.

5. A peptide-containing graft copolymer according to claim 1 wherein said polymeric backbone containing free primary or secondary amine functional units exhibits a pK of at least about 8.

6. A peptide-containing graft copolymer according to claim 1 wherein the polymeric backbone containing free primary or secondary amine functional units exhibits a pK of from about 8.5 to about 10.

7. A peptide-containing graft copolymer according to claim 1 wherein said backbone comprises monomer units containing free primary or secondary amine functional groups, which amine groups are present in an amount of at least about 1-25 millimoles free amine group/gram polymer containing said amine groups for reaction with said amino acid or peptide graft.

8. A peptide-containing graft copolymer according to claim 1 wherein said backbone exhibits a number average molecular weight of from about 10,000 to about 250,000.

9. A peptide-containing graft copolymer according to claim 1 wherein said polymeric backbone is selected from the group consisting of polylysine, polyallylamine, polyethylenimine, chitosan, polyvinylamine, chrondroitin sulfate, polydextran, hyaluronic acid, polyacrylic acid, and copolymers of any of the copolymerizable monomers thereof.

10. A peptide-containing graft copolymer according to claim 1 wherein said polymeric backbone is polylysine.

11. A peptide-containing graft copolymer according to claim 1 wherein said polymeric backbone is polyallylamine.

12. A peptide-containing graft copolymer according to claim 10 wherein from at least about 5% to about 30% of said free primary or secondary free amine groups are reacted with said amino acid or peptide graft.

13. A peptide-containing graft copolymer according to claim 10 wherein from about 10% to about 20% of said free primary or secondary amine groups are reacted with said amino acid or peptide graft.

14. A peptide-containing graft copolymer according to claim 11 wherein from at least about 5% to about 30% of said free primary or secondary free amine groups are reacted with said amino acid or peptide graft.

15. A peptide-containing graft copolymer according to claim 11 wherein from about 10% to about 20% of said free primary or secondary amine groups are reacted with said amino acid or peptide graft.

16. A peptide-containing graft copolymer according to claim 1 wherein said amino acid or peptide graft comprises 3,4-dihydroxyphenylalanine (Dopa) amino acid.

17. A peptide-containing graft copolymer according to claim 1 wherein said amino acid or peptide graft comprises a precursor of 3,4-dihydroxyphenylalanine capable of hydroxylation to the Dopa form.

18. A peptide containing graft copolymer according to claim 17, wherein said precursor is selected from the group consisting of tyrosine and phenylalanine.

19. A peptide-containing graft copolymer according to claim 1 wherein said amino acid or peptide graft is selected from the group consisting of Dopa, Dopa-Lys-Ala-Lys, Hyp-Hyp-Thr-Dopa-Lys, Ala-Lys-Pro-Ser-Dopa, Dopa-Hyp-Hyp-Thr, Hyp-Thr-Dopa-Lys, Dopa-Hyp-Lys-Ser, Dopa-Lys-Ala-Lys-Hyp-Ser-Tyr, Dopa-Lys-Ala-Lys-Hyp-Ser-Tyr-Hyp-Hyp-Thr, Lys-Hyp-Ser-Dopa-Hyp-Hyp-Thr-Dopa-Lys, Dopa-Lys-Glu-Ser-Hyp, Dopa-Lys-Cys(SO₃ H)-Lys, Cys(SO₃)-Lys-Pro-Ser-Tyr-Hyp-Hyp-Thr-Dopa-Lys, and Lys-Dopa-Thr-Hyp-Hyp-Tyr-Ser-Pro-Lys-Ala, Hyp-Hyp-Thr-Tyr-Lys, Ala-Lys-Pro-Ser-Typ, Phe-Tyr-Lys-Ser, and Hyp-Hyp-Thr-Phe-Lys.

20. A peptide-containing graft copolymer according to claim 1 wherein said polymeric backbone is polylysine and said amino acid or peptide graft is selected from the group consisting of Lys-Dopa-Thr-Hyp-Hyp-Tyr-Ser-Pro-Lys-Ala, Lys-Pro-Ser-Tyr-Hyp-Hyp-Thr-Dopa-Lys, Lys-Hyp-Ser-Dopa-Hyp-Hyp-Thr-Dopa-Lys, Ala-Lys-Pro-Ser-Tyr-Hyp-Thr-Dopa-Lys, Dopa-Lys-Ala-Lys-Pro-Ser-Tyr, Dopa-Lys-Ala-Lys-Ala-Lys-Hyp-Ser-Dopa-Hyp-Hyp-Thr and Dopa.

21. A peptide-containing graft copolymer according to claim 1 wherein said polymeric backbone is polyallylamine and said amino acid or peptide graft is selected from the group consisting of Dopa, Lys-Pro-Ser-Tyr-Hyp-Hyp-Thr-Dopa-Lys, Cys-Pro-Ser-Thr-Pro-Pro-Thr-Thr-Lys, Hyp-Thr-Dopa-Lys, Dopa-Lys-Ala-Lys-Pro-Ser-Tyr, and Dopa-Lys-Ala-Lys-Hyp-Ser-Dopa-Hyp-Hyp-Thr.

22. A peptide-containing graft copolymer according to claim 1 wherein said polymeric backbone is polyallylamine and said amino acid or peptide graft is Dopa.

23. A peptide-containing graft copolymer according to claim 1 wherein said polymeric backbone is polyallylamine and said amino acid or peptide graft is SA-Lys-Pro-Tyr-Hyp-Hyp-Thr-Dopa-Lys-OH.

24. A water-soluble cationic peptide-containing graft copolymer exhibiting a molecular weight of from about 30,000 to about 500,000 comprising:

(a) a polymeric backbone comprising monomer repeat units, each of said monomer repeat units including or capable of modification to include free primary or secondary amine functional units for reaction with an amino acid or peptide graft, said polymeric backbone exhibiting a number average molecular weight of from about 10,000 to about 250,000; and

(b) an amino acid or peptide graft reacted with at least 5% of said primary or secondary amine functional units of said polymeric backbone, wherein said amino acid or peptide graft comprises at least one 3,4-dihydroxyphenyalanine (Dopa) amino acid or precursor thereof capable of hydroxylation to the Dopa form.

25. A water soluble cationic peptide-containing graft copolymer according to claim 24 wherein said monomer repeat units are selected from the group consisting of lysine and allylamine.

26. A water soluble cationic peptide-containing graft copolymer according to claim 24 wherein the free primary or secondary amine functional units are present in an amount of at least about 1-25 millimoles amine/gram of polymer for reaction with said amino acid or peptide graft.