Functionalized polymers

1. A conjugate, or a pharmaceutically acceptable salt thereof, comprising a water-soluble, non-peptidic, and non-nucleotidic polymer backbone having at least one terminus covalently bonded to a structure of formula (7):

wherein:

A is the point of covalent bonding to the terminus of the polymer backbone, wherein the polymer backbone is poly(ethylene glycol), wherein said poly(ethylene glycol) has an average molecular weight from about 500 Da to about 100,000 Da;

E is O;

Y represents an optionally substituted residue selected from the group consisting of alkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl;

Z 1 and Z 2 are O;

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

M is a biologically active molecule or a detectable functional group.

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

3. The conjugate of claim 1 , wherein only one termini of the polymer backbone is covalently bonded to the structure of formula (7).

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

5. The conjugate of claim 4 , wherein only one termini of the polymer backbone is covalently bonded to the structure of formula (7).

6. The conjugate of claim 4 , wherein both termini of the polymer backbone are covalently bonded to the structure of formula (7).

7. The conjugate of claim 1 , wherein said biologically active molecule is selected from the group consisting of enzymes, peptides, polypeptides, nucleotides, oligonucleotides, polynucleotides, and therapeutic agents having a molecular weight of less than 1000 g/mol.

8. A method of preparing a conjugate, or a pharmaceutically acceptable salt thereof, comprising a water-soluble, non-peptidic, and non-nucleotidic polymer backbone having at least one terminus covalently bonded to a structure of formula (7):

or a salt thereof,

wherein:

A is the point of covalent bonding to the terminus of the polymer backbone, wherein the polymer backbone is poly(ethylene glycol), wherein said poly(ethylene glycol) has an average molecular weight from about 500 Da to about 100,000 Da;

E is O;

Y represents an optionally substituted residue selected from the group consisting of alkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl;

Z 1 and Z 2 are O;

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

M is a biologically active molecule;

comprising the steps of:

(a) providing a compound of formula (8):

wherein:

A is the point of covalent bonding to the terminus of the polymer backbone, wherein the polymer backbone is poly(ethylene glycol), wherein said poly(ethylene glycol) has an average molecular weight from about 500 Da to about 100,000 Da;

E is O;

Y represents an optionally substituted residue selected from the group consisting of alkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl;

Z 1 and Z 2 are O;

L 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 group that when deprotected is reactive with a biologically active molecule;

R is a hydrophobic separation handle;

R 1 is absent or a hydrophobic separation handle;

(b) removing the hydrophobic separation handle(s);

(c) optionally reacting the compound obtained in step (b) with an activating agent; and

(d) reacting the compound obtained in step (b), or, optionally in step (c), with a biologically active molecule to prepare the conjugate.

9. The method of claim 8 , wherein the protected group M in formula (8) is, when deprotected, 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, and iodoacetamide.

10. The method of claim 8 , wherein R is selected from the group consisting of: trityl, monoalkoxytrityl, dialkoxytrityl, pixyl, alkoxypixyl, fluorenylmethyloxycarbonyl, trifluoroacetyl, acetal, and cyclic acetal.

11. The method of claim 8 , wherein reaction step (d) is carried out in the presence of water or a protic solvent.

12. The method of claim 8 , wherein the compound of formula (8) is essentially pure.

13. The method of claim 8 , wherein the biologically active material or the detectable functional group reacts acidic in water.

14. The method of claim 8 , wherein the polymer has from 2 to 100 termini.

15. The method of claim 8 , wherein only one termini of the polymer backbone is covalently bonded to the structure of formula (7).

16. The method of claim 8 , wherein the polymer backbone has two termini.

17. The method of claim 16 , wherein only one termini of the polymer backbone is covalently bonded to the structure of formula (7).

18. The method of claim 16 , wherein both termini of the polymer backbone are covalently bonded to the structure of formula (7).

19. The method of claim 8 , wherein said biologically active molecule is selected from the group consisting of enzymes, peptides, polypeptides, nucleotides, oligonucleotides, polynucleotides, and therapeutic agents having a molecular weight of less than 1000 g/mol.