Chemical modification of recombinant interleukin 2 by polyethylene glycol increases its potency in the murine Meth A sarcoma model.
Recombinant human interleukin 2 purified from Escherichia coli has limited solubility at neutral pH and a short circulatory half-life. This recombinant interleukin 2 was chemically modified by an active ester of polyethylene glycol. The modified interleukin 2 was purified by hydrophobic interaction chromatography and characterized by sodium dodecyl sulfate/polyacrylamide gel electrophoresis and isoelectric focusing. This conjugate was compared to unmodified recombinant interleukin 2 in vitro and in vivo. Covalent attachment of the hydrophilic polymer polyethylene glycol enhanced the solubility of interleukin 2, decreased its plasma clearance, and increased its antitumor potency in the Meth A murine sarcoma model.
D000818:Animals; D005260:Female; D006863:Hydrogen-Ion Concentration; D007376:Interleukin-2; D007525:Isoelectric Focusing; D007700:Kinetics; D008748:Methylcholanthrene; D051379:Mice; D008807:Mice, Inbred BALB C; D011092:Polyethylene Glycols / Q000494:pharmacology*; D011994:Recombinant Proteins / Q000378:metabolism / Q000494:pharmacology; D012513:Sarcoma, Experimental / Q000188:drug therapy*; D013329:Structure-Activity Relationship
D007376:Interleukin-2; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D008748:Methylcholanthrene