Functionalized polymers

1. A compound comprising a water-soluble, non-peptidic, and non-nucleotidic polymer backbone having at least one terminus covalently bonded to a structure of formula (1):

or a salt thereof,

wherein:

A is the point of covalent bonding to the terminus of the polymer backbone;

E is O;

K is selected from the group consisting of: alkylene, alkyleneoxyalkylene, and oligomeric alkyleneoxyalkylene;

G is selected from the group consisting of: hydrogen, alkoxy, and a hydrophobic separation handle;

Z 1 and Z 2 are independently O;

L is a divalent radical of an alkylene;

M is a protected carboxyl moiety;

R is selected from the group consisting of: a protecting group and a hydrophobic separation handle;

R 1 is absent or a hydrophobic separation handle;

and

wherein no more than one of R, R 1 , and G is a hydrophobic separation handle.

2. The compound of claim 1 , wherein the polymer has from 2 to 100 termini.

3. The compound of claim 1 , wherein only one termini of the polymer backbone is covalently bonded to the structure of formula (1).

4. The compound of claim 1 , wherein the polymer backbone has two termini.

5. The compound of claim 4 , wherein only one termini of the polymer backbone is covalently bonded to the structure of formula (1).

6. The compound of claim 4 , wherein both termini of the polymer backbone are covalently bonded to the structure of formula (1).

7. The compound of claim 1 , wherein K is selected from the group consisting of: methylene, ethylene, propylene, isopropylene, butylene, isobutylene, sec-butylene, tert-butylene, and hexylene, or a residue from diethylene glycol, triethylene glycol, tetraethylene glycol or hexaethylene glycol.

8. The compound of claim 1 , wherein G is a substituted or unsubstituted trityloxy.

9. The compound of claim 1 , wherein L is a substituted or unsubstituted C 1 -C 12 alkylene.

10. The compound claim 1 , wherein R is selected from the group consisting of: trityl, monoalkoxytrityl, dialkoxytrityl, pixyl, alkoxypixyl, fluorenylmethyloxycarbonyl, trifluoroacetyl, acetal, and cyclic acetal.

11. The compound of claim 1 , wherein R is selected from the group consisting of: chlorotrityl, trityl, N-hydroxysuccinimidyl, p-nitrophenyl, pentachlorophenyl, and an unsubstituted C 1 -C 18 alkyl.

12. The compound of claim 1 , wherein said polymer backbone is selected from the group consisting of poly(alkylene glycol), poly(oxyethylated polyol), poly(olefinic alcohol), poly(α-hydroxy acid), poly(vinyl alcohol), polyoxazoline, and copolymers.

13. The compound of claim 1 , wherein said polymer backbone is poly(ethylene glycol).

14. The compound of claim 13 , wherein said poly(ethylene glycol) has an average molecular weight from about 500 Da to about 100,000 Da.

15. A preparation comprising a compound comprising a water-soluble, non-peptidic, and non-nucleotidic polymer backbone having at least one termini covalently bonded to a structure of formula (1):

or a salt thereof,

wherein:

A is the point of bonding to the terminus of the polymer backbone;

E is O;

K is selected from the group consisting of: alkylene, alkyleneoxyalkylene, and oligomeric alkyleneoxyalkylene;

G is selected from the group consisting of: hydrogen, alkoxy, and a hydrophobic separation handle;

Z 1 and Z 2 are independently O;

L is a divalent radical of an alkylene;

M is a protected carboxyl moiety;

R is selected from the group consisting of: a protecting group and a hydrophobic separation handle;

R 1 is absent or a hydrophobic separation handle;

provided that only one of R and R 1 is a hydrophobic separation handle or the hydrophobicity of one of R or R 1 is higher than the other;

wherein said preparation comprises at least 50% by weight of said compound; and

wherein no more than one of R, R 1 , and G is a hydrophobic separation handle.

16. The preparation of claim 15 , wherein the compound is essentially pure.

17. A compound of formula (2):

or a salt form thereof,

wherein:

polymer is a linear, water-soluble, non-peptidic, and non-nucleotidic polymer backbone, wherein each linking group is bonded at a different terminus of said polymer;

E is O; and

E 1 is O or S;

K and K 1 are independently selected from the group consisting of: alkylene, alkyleneoxyalkylene, and oligomeric alkyleneoxyalkylene;

G and G 1 are independently absent or are selected from the group consisting of: alkoxy and a hydrophobic separation handle;

Z 1 and Z 2 independently are O;

Z 3 and Z 4 are independently selected from O and NH, wherein no more than one of Z 3 and Z 4 is NH;

L is a divalent radical of a alkylene;

L 1 is selected from the group consisting of: a divalent radical of a nucleoside, alkylene, alkyleneoxyalkylene, oligomeric alkyleneoxyalkylene, and unsubstituted and substituted arylene;

M is a protected carboxyl moiety;

M 1 is selected from a protected group that when deprotected is reactive with a biologically active molecule, a group reactive with a biologically active molecule, or a detectable functional group;

wherein M and M 1 are different;

R is a protecting group;

R 1 is absent, hydrogen, a protecting group, or an activating group;

wherein when M 1 is a protected group that when deprotected is reactive with a biologically active molecule, then R 1 is a protecting group or a hydrophobic separation handle;

wherein when M 1 is a group reactive with a biologically active molecule, R 1 is absent, hydrogen, or an activating group; and

wherein when M 1 is a detectable functional group, R 1 is absent or hydrogen.

18. A preparation comprising a compound of formula (2):

or a salt form thereof,

wherein:

polymer is a linear, water-soluble, non-peptidic, and non-nucleotidic polymer backbone, wherein each phosphonate-derived functional group is bonded at a different terminus of said polymer;

E is O; and

E 1 is O or S;

K and K 1 are independently selected from the group consisting of: alkylene, alkyleneoxyalkylene, and oligomeric alkyleneoxyalkylene;

G and G 1 are independently absent or are selected from the group consisting of: alkoxy and a hydrophobic separation handle;

Z 1 and Z 2 independently are O;

Z 3 and Z 4 are independently selected from O and NH, wherein no more than one of Z 3 and Z 4 is NH;

L is a divalent radical of a alkylene;

L 1 is selected from the group consisting of: a divalent radical of a nucleoside, alkylene, alkyleneoxyalkylene, oligomeric alkyleneoxyalkylene, and unsubstituted and substituted arylene;

M is a protected carboxyl moiety;

M 1 is selected from a protected group that when deprotected is reactive with a biologically active molecule, a group reactive with a biologically active molecule, or a detectable functional group;

wherein M and M 1 are different;

R is a protecting group;

R 1 is absent, hydrogen, a protecting group, or an activating group;

wherein when M 1 is a protected group that when deprotected is reactive with a biologically active molecule, then R 1 is a protecting group or a hydrophobic separation handle;

wherein when M 1 is a group reactive with a biologically active molecule, R 1 is absent, hydrogen, or an activating group; and

wherein when M 1 is a detectable functional group, R 1 is absent or hydrogen; and

wherein said preparation comprises at least 50% by weight of said compound.

19. A compound of formula (3):

or a salt form thereof,

wherein:

polymer is a linear, water-soluble, non-peptidic, and non-nucleotidic polymer backbone, wherein M 2 and the phosphonate-derived functional group are bonded at a different terminus of said polymer;

E is O;

E 1 is O or S;

K is selected from the group consisting of: alkylene, alkyleneoxyalkylene, and oligomeric alkyleneoxyalkylene;

G is selected from the group consisting of: hydrogen, alkoxy, and a hydrophobic separation handle;

Z 1 and Z 2 are independently O;

L is a divalent radical of an alkylene;

M is a protected carboxyl moiety;

M 2 is selected from O, S or NH; and

R is a protecting group or a hydrophobic separation handle;

R 2 is hydrogen or a protecting group.

20. A preparation comprising a compound of formula (3):

or a salt form thereof,

wherein:

polymer is a linear, water-soluble, non-peptidic, and non-nucleotidic polymer backbone, wherein M 2 and the phosphonate-derived functional group are bonded at a different terminus of said polymer;

E is O and E 1 is O or S;

K is selected from the group consisting of: alkylene, alkyleneoxyalkylene, and oligomeric alkyleneoxyalkylene;

G is selected from the group consisting of: hydrogen, alkoxy, and a hydrophobic separation handle;

Z 1 and Z 2 are independently O;

L is a divalent radical of an alkylene;

M is a protected carboxyl moiety;

M 2 is selected from O, S or NH; and

R is a protecting group or a hydrophobic separation handle;

R 2 is hydrogen or a protecting group;

and

wherein said preparation comprises at least 50% of said compound.

21. The compound of claim 1 , wherein the hydrophobicity of one of R or R 1 is higher than the other.

22. The compound of claim 17 , wherein one of Z 3 and Z 4 is NH and the other is O.

23. The compound of claim 17 , wherein Z 3 is O and Z 4 is O.

24. The compound of claim 17 , wherein said group reactive with a biologically active molecule is selected from the group consisting of: hydroxyl, amine, thiol, carboxyl, aldehyde, glyoxal, dione, alkenyl, alkynyl, alkedienyl, azide, acrylamide, vinyl sulfone, hydrazide, aminoxy, maleimide, dithiopyridine, iodoacetamide.

25. The compound of claim 17 , wherein K or K 1 is independently selected from the group consisting of: methylene, ethylene, propylene, isopropylene, butylene, isobutylene, sec-butylene, tert-butylene, and hexylene, or a residue from diethylene glycol, triethylene glycol, tetraethylene glycol or hexaethylene glycol.

26. The compound of claim 17 , wherein G or G 1 is independently a substituted or unsubstituted trityloxy.

27. The compound of claim 17 , wherein L 1 is a substituted or unsubstituted C 1 -C 12 alkylene.

28. The compound of claim 17 , wherein R or R 1 is independently selected from the group consisting of: trityl, monoalkoxytrityl, dialkoxytrityl, pixyl, alkoxypixyl, fluorenylmethyloxycarbonyl, trifluoroacetyl, acetal, cyclic acetal, and combinations of thereof.

29. The compound of claim 17 , wherein said polymer is poly(ethylene glycol).

30. The compound of claim 29 , wherein said poly(ethylene glycol) has an average molecular weight from about 500 Da to about 100,000 Da.

31. The compound of claim 19 , wherein G is a substituted or unsubstituted trityloxy group.

32. The compound of claim 31 , wherein G is selected from a monoalkoxy substituted trityloxy group or dialkoxy substituted trityloxy group.

33. The compound of claim 19 , wherein said group reactive with a biologically active molecule is selected from the group consisting of: hydroxyl, amine, thiol, carboxyl, aldehyde, glyoxal, dione, alkenyl, alkynyl, alkedienyl, azide, acrylamide, vinyl sulfone, hydrazide, aminoxy, maleimide, dithiopyridine, iodoacetamide.

34. The compound of claim 19 , wherein R 2 is absent or selected from the group consisting of trityl, monoalkoxytrityl, dialkoxytrityl, pixyl, alkoxypixyl, fluorenylmethyloxycarbonyl, alkylcarboxyl, benzoyl, tetrahydropyranyl, methyl.

35. The compound of claim 19 , wherein said polymer is poly(ethylene glycol).