A new procedure for the synthesis of polyethylene glycol-protein adducts; effects on function, receptor recognition, and clearance of superoxide dismutase, lactoferrin, and alpha 2-macroglobulin.
A new, simplified technique for the synthesis of polyethylene glycol (PEG) derivatives of proteins utilizing 1,1'-carbonyldiimidazole for PEG activation, is described. PEG derivatives of superoxide dismutase, alpha 2-macroglobulin, alpha 2-macroglobulin-trypsin, and lactoferrin were prepared and studied. Superoxide dismutase coupled to PEG preserved 95% of its original activity while its plasma half-life increased from 3.5 min to 9 or more hours depending on the PEG derivative studied. PEG-derivatized alpha 2-macroglobulin showed decreased protease binding activity but PEG derivatives of performed alpha 2-macroglobulin-trypsin demonstrated no loss of activity. The plasma clearance of PEG-alpha 2-macroglobulin-trypsin was prolonged significantly compared to native alpha 2-macroglobulin-trypsin, particularly when a high-molecular-weight PEG was coupled to the protease inhibitor complex. The plasma clearance half-life of lactoferrin was increased 5- to 20-fold by this modification. Trinitrobenzenesulfonic acid titration studies demonstrated that epsilon-amino groups of lysine residues are modified by the coupling of carbonyldiimidazole-activated PEG to proteins.
Beauchamp, CO; Gonias, SL; Menapace, DP; Pizzo, SV
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