Cyclic imide thione activated polyalkylene oxides

A method of forming a biologically active conjugate of a biologically active nucleophile and one or more water-soluble polyalkylene oxides covalently bonded thereto, said method comprising the steps of:

• contacting a biologically active nucleophile with a cyclic imide thione activated polyalkylene oxide, so that a biologically active conjugate of said biologically active nucleophile and said polyalkylene oxide is formed;
• and
• recovering said biologically active conjugate, wherein said cyclic imide thione activated polyalkyleneoxide has a structure represented by:
• X--R--L--CO--R.sub.3
• wherein R is a polyalkyleneoxide residue having a number average molecular weight between 600 and 100,000 daltons;
• R3 is selected from the group consisting of:
• ##STR7## L is moiety forming a covalent linkage between R and the carbonyl carbon, said moiety being hydrolytically stable at physiologic pH and temperatures up to 27 degrees celsius;
• and
• X is a terminal moiety of said polyoxyalkyleneoxide.