Patent ID: 7901665

Claim:
A method of conjugating a carboxylate-containing molecule to an amine-containing macromolecule in a multiphasic solution to form a substituted macromolecule comprising: (a) forming a first solution by dissolving at least one amine-containing macromolecule in an aqueous basic solution; (b) forming a second solution by combining at least one carboxylate-containing molecule with at least one acid acceptor in an aprotic organic solvent; (c) adding at least one carboxylate-activating agent to the second solution to form an activated carboxylate-containing molecule; (d) generating a multiphasic solution by mixing the first solution and the second solution in the presence of sodium chloride, wherein the sodium chloride is present at a concentration of 2 molar; and (e) forming the substituted macromolecule in the multiphasic solution.