Multiarmed, monofunctional polymer for coupling to molecules and surfaces

摘要

Multi-armed, monofunctional, and hydrolytically stable polymers are described having the structure wherein Z is a moiety that can be activated for attachment to biologically active molecules such as proteins and wherein P and Q represent linkage fragments that join polymer arms polya and polyb, respectively, to central carbon atom, C, by hydrolytically stable linkages in the absence of aromatic rings and ester groups in the linkage fragments. R typically is hydrogen or methyl, but can be a linkage fragment that includes another polymer arm. A specific example is an mPEG disubstituted lysine having the structure where mPEGa and mPEGb have the structure CH3O-(CH2CH2O)nCH2CH2- wherein n may be the same or different for mPEGa and mPEGb and can be from 1 to about 1,150 to provide molecular weights of from about 100 to 100,000. The mPEG disubstituted lysine can be purified from a reaction mixture by chromatography in water, including gel filtration chromatography and ion exchange chromatography because the carboxyl group is ionizable. Impurities are removed, including unreacted mPEG and mPEG monosubstituted lysine, to provide the polymer in pure form. Ion exchange chromatography permits fractionation of a greater amount of polymer per run.