BRANCHED POLYMERS
The present invention is directed to branched reactive water-soluble polymers comprising at least two polymer arms, such as poly(ethylene glycol), attached to a central aliphatic hydrocarbon core molecule through heteroatom linkages. The branched polymers bear at least one functional group for reacting with a biologically active agent to form a biologically active conjugate. The functional group of the branched polymer can be directly attached to the aliphatic hydrocarbon core or via an intervening linkage, such as a heteroatom, -alkylene-, —O-alkylene-O—, -alkylene-O-alkylene-, -aryl-O—, —O-aryl-, (—O-alkylene-) m , or (-alkylene-O—) m linkage, wherein m is 1-10.
1 . A branched reactive polymer having a structure:
wherein:
R is a linear aliphatic hydrocarbon having a length of 3, 5, or 7 carbon atoms;
each polymer arm, POLY, is —CH 2 CH 2 O(CH 2 CH 2 O) n —OH or —CH 2 CH 2 O(CH 2 CH 2 ) n —OCH 3 , and is attached, via X′, to a different carbon atom of R to provide a branched reactive polymer in which the polymer arms are symmetrically positioned on the linear aliphatic hydrocarbon with respect to one another and the para-NO 2 —(C 6 H 5 )OC(O)O—(X) p group to thereby provide a symmetrical branched reactive polymer;
X′ is a heteroatom linkage selected from the group consisting of —NH—, —O— and —S—, wherein X′ in each of (X′-POLY) q is the same;
X is a linker of from one to ten atoms;
p is 0 or 1;
n is from about 5 to about 1,200;
q is 3, 4, or 5;
and further wherein the branched reactive polymer has a molecular weight of about 500 Da to about 100,000 Da
2 . The branched reactive polymer of claim 1 , wherein X′ is —O—.
3 . The branched reactive polymer of claim 1 , wherein q is 3.
4 . The branched reactive polymer of claim 1 , wherein the carbon atom of the linear aliphatic hydrocarbon to which (X) p —OC(O)O-para-C 6 C 4 —NO 2 is attached does not possess a polymer arm attached thereto.
5 . The branched reactive polymer of claim 1 , wherein R comprises 7 carbon atoms.
6 . The branched reactive polymer of claim 1 , wherein R comprises three carbon atoms.
7 . The branched reactive polymer of claim 1 , wherein each POLY is identical.
8 . The branched reactive polymer of claim 1 , wherein p is 1 and X is selected from the group consisting of linear C1-C3 alkylene, C1-C3 alkylene-O—C1-C3 alkylene, -phenylene-O—, and (C1-C3 alkylene-O—) 1-3 .
9 . The branched reactive polymer of claim 1 , wherein p is zero.
10 . The branched reactive polymer of claim 1 , having a molecular weight of about 5,000 Da to about 60,000 Da.
11 . The branched reactive polymer of claim 1 , wherein each POLY is —CH 2 CH 2 O(CH 2 CH 2 ) n —OCH 3 .
12 . The branched polymer of claim 1 , wherein the aliphatic hydrocarbon contains 5 carbon atoms.
13 . The branched polymer of claim 38 , wherein each of the polymer arms extending from the linear aliphatic hydrocarbon is identical.
14 . The branched polymer of claim 1 , wherein q is 5.