Method involving 1-benzotriazolyl carbonate esters of poly(ethylene glycol)
View Patent ↗The invention provides a method comprising the steps of providing a poly(ethylene glycol) 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 an amino acid to form an amino acid derivative; and reacting the amino acid derivative with a biologically active agent under conditions to form a polymer-active agent conjugate.
1. A method comprising;
providing a poly(ethylene glycol)l 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 selected from the group consisting of H, N-succinimidyl, and 1-benzotriazolyl; and
reacting the amino acid derivative with a biologically active agent under conditions to form a polymer-active agent conjugate.
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.
4. The method of claim 1 , wherein the biologically active agent is a protein.