COVALENT ATTACHMENT OF POLY(ETHYLENEGLYCOL) TO PEPTIDES AND PROTEINS - REEVALUATION OF THE SYNTHESIS, PROPERTIES, AND USEFULNESS OF CARBONYLIMIDAZOL-1-YL-METHOXYPOLY(ETHYLENEGLYCOL)

Carbonylimidazol-1-yl-mPEG is obtained quantitatively by reacting meth oxypoly(ethyleneglycol) (mPEG) with 1.1 Eq of N-N'-carbonyldiimidazole in the presence of a stoechiometric amount of 4-dimethyl-aminopyridin e used as hypernucleophilic acylation catalyst. Carbonylimidazol-1-yl- mPEG is quite stable in aqueous solutions with half-lives up to 70 h i n pHs ranging from 6.0 to 7.0 at 25-degrees-C. From reactivity studies toward amines with various nucleophilic strengths, it is suggested th at carbonylimidazol-1-yl-mPEG may be best used to modify alpha-amino t erminal function of proteins selectively or to introduce amino functio n on PEG chains.