| abstract |
Methods are provided for the synthesis of polymer conjugates of cytokines, chemokines, growth factors, polypeptide hormones and receptor-~binding antagonists thereof, which conjugates retain unusually high receptor~-bindin g activity. Preparation of polymer conjugates according to the methods of the present invention diminishes or avoids steric inhibition of receptor-~ligand interactions that commonly results from the attachment of polymers to recept or- binding regions of cytokines, chemokines, growth factors and polypeptide hormones, as well as to agonistic and antagonistic analogs thereof. The invention also provides conjugates and compositions produced by such methods . The conjugates of the present invention retain a higher level of receptor- binding activity than those produced by traditional polymer coupling methods that are not targeted to avoid receptor-binding domains of cytokines, chemokines, growth factors and polypeptide hormones. The conjugates of the present invention also exhibit an extended half-life in vivo and in vitro compared to unconjugated cytokines, chemokines, growth factors and polypepti de hormones. The present invention also provides kits comprising such conjugate s and/or compositions, and methods of use of such conjugates and compositions in a variety of diagnostic,prophylactic, therapeutic and bioprocessing applications. |