Branched polymers and their conjugates

A biologically active conjugate comprising a branched polymer covalently attached to a biologically active molecule, wherein the conjugate has the structure:

• D-L1-(X)p-R(-X′-POLY)q
• wherein:
• D is the biologically active molecule;
• L1 is a linkage resulting from the reaction of a functional group of the branched polymer and a functional group of the biologically active molecule;
• R is an aliphatic hydrocarbon having a length of at least three carbon atoms;
• each POLY is a water soluble and non-peptidic polymer;
• X′ is a heteroatom linkage;
• X is a linker;
• p is 0 or 1;
• and
• q is 2 to about 10.

A nucleophile-substituted aliphatic hydrocarbon core molecule having the structure:

• Y′—(X)p-R(-Nu)q
• wherein:
• Y′ is a protected functional group;
• each Nu is a nucleophile;
• R is an aliphatic hydrocarbon having a length of at least three carbon atoms;
• X is a linker;
• p is 0 or 1;
• and
• q is 2 to about 10.

A method of preparing a branched poly(alkylene glycol) polymer, comprising:

• providing an aliphatic hydrocarbon substituted with at least two nucleophilic groups and at least one protected functional group;
• polymerizing alkylene oxide monomer units onto the aliphatic hydrocarbon at the site of the nucleophilic groups to form at least two poly(alkylene glycol) polymers attached to the aliphatic hydrocarbon via heteroatom linkages;
• end-capping the poly(alkylene glycol) polymers with an alkyl group to form alkoxy-terminated polymers;
• and
• deprotecting the protected functional group to form a hydroxyl group.