Coupling of monomethoxypolyethyleneglycols to proteins via active esters.
Two alternative methods for the attachment of monomethoxypolyethyleneglycols (PEG) to proteins are proposed; they are based upon the replacement of the hydroxy terminal function of PEG to carboxylate followed by its activation with dicyclohexylcarbodiimide and N-hydroxysuccinimide. The methods, which give more homogeneous product than that employing trichloro-s-triazine as coupling reagent, may also be used for the modification of essential -SH containing enzymes. The attachment of PEG activated via esters was tested with several model proteins and the influence of the extent of modification i. on the biological activity of various enzymes, ii. on the binding capacity for albumin and iii. on the clearance time in rats using superoxide dismutase as model tracer was evaluated. It was also demonstrated that the extent of PEG attachment varies greatly according to the different proteins used.
D000818:Animals; D001798:Blood Proteins; D002374:Catalase; D002417:Cattle; D055598:Chemical Phenomena; D002621:Chemistry; D004912:Erythrocytes / Q000201:enzymology; D004952:Esters; D006801:Humans; D008099:Liver / Q000201:enzymology; D011092:Polyethylene Glycols; D011485:Protein Binding; D011506:Proteins; D012710:Serum Albumin, Bovine; D013482:Superoxide Dismutase / Q000097:blood
D001798:Blood Proteins; D004952:Esters; D011506:Proteins; D012710:Serum Albumin, Bovine; D011092:Polyethylene Glycols; C028210:monomethoxypolyethylene glycol; D002374:Catalase; D013482:Superoxide Dismutase