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 PROCEDURE FOR THE SYNTHESIS OF POLYETHYLENE GLYCOL-PROTEIN ADDUCTS - EFFECTS ON FUNCTION, RECEPTOR RECOGNITION, AND CLEARANCE OF SUPEROXIDE-DISMUTASE, LACTOFERRIN, AND ALPHA-2-MACROGLOBULIN
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DOI：
10.1016/0003-2697(83)90131-8
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发表时间：
1983-01-01
影响因子：
2.9
通讯作者：
PIZZO, SV
中科院分区：
文献类型：
--
作者：
BEAUCHAMP, CO;GONIAS, SL;PIZZO, SV
A new, simplified technique for the synthesis of polyethylene glycol (PEG) derivatives of proteins [for use as drugs] utilizing 1,1''-carbonyldiimidazole for PEG activation, is described. PEG derivatives of [bovine liver] superoxide dismutase, [human plasma] .alpha.2-macroglobulin, .alpha.2-macroglobulin-trypsin, and [human milk] lactoferrin were prepared and studied. Superoxide dismutase coupled to PEG preserved 95% of its original activity while its plasma half-life [in mice] 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 preformed .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 carbonyldimiidazole-activated PEG to proteins.
