Polymer-active agent conjugate
The invention provides for preparing a polymer-active agent conjugate, the method comprising the steps of reacting an amino acid derivative with a biologically active agent under conditions to form a polymer-active agent conjugate.
1. A polymer-active agent conjugate, the polymer-active agent conjugate prepared by a method comprising:
reacting a polymeric amino acid derivative with a biologically active agent under conditions to form a polymer-active agent conjugate,
wherein the polymeric amino acid derivative was prepared by a method comprising:
providing a linear poly(ethylene glycol) having one terminal hydroxyl group and having a molecular weight of about 20,000 daltons;
reacting the terminal hydroxyl group of the poly(ethylene glycol) with di(1-benzotriazolyl) carbonate to form a 1-benzotriazolylcarbonate ester of the poly(ethylene glycol);
reacting the 1-benzotriazolylcarbonate ester of the poly(ethylene glycol) with lysine to form in one or more steps a polymeric amino acid derivative, said polymeric amino acid derivative having the following structure:
wherein:
PEG is a linear poly(ethylene glycol) having a molecular weight of about 20,000 daltons,
Z is N-succinimidyl, and
the biologically active agent is an oligonucleotide.
2. The polymer-active agent conjugate of claim 1 , wherein each PEG is capped with a capping group.
3. The polymer-active agent conjugate of claim 2 , wherein the capping group is methoxy.