Method involving 1-benzotriazolyl carbonate esters of poly(ethylene glycol)
View Patent ↗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 method for preparing a polymer-active agent conjugate, the method comprising:
reacting an amino acid derivative with a biologically active agent under conditions to form a polymer-active agent conjugate,
wherein the amino acid derivative was prepared by a method comprising:
providing a poly(ethylene glycol)1 having one terminal hydroxyl group;
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 an amino acid derivative, said amino acid derivative having the following structure:
wherein PEG is a poly(ethylene glycol), and Z is N-succinimidyl, and wherein the biologically active agent is an oligonucleotide.
2. The method of claim 1 , wherein each PEG is capped with a capping group.
3. The method of claim 2 , wherein the capping group is methoxy.