Synthesis of conjugates of 1-(carboxymethyl)cytosine and 1-(5-O-carboxymethyl-β-D-arabinofuranosyl)cytosine with proteins

1-(Carboxymethyl)cytosine (Ia), 1-(5-O-carboxymethyl-β-D-arabinofuranosyl)cytosine (IIa) and 5'-O-carboxylmethylcytidine (IIIa) were transformed by treatment with acetic anhydride and 4-dimethylaminopyridine to the peracetyl derivatives Ib-IIIb. These products reacted with p-nitrophenol in the presence of N, N'-dicyclohexylcarbodiimide to give the activated esters Ic-IIIc which on reaction with ammonia, dimethylamine or 2-aminoethanol afforded the corresponding carboxamides Id-IIId, IIe,f. Reactions of Ic and IIc with human serum albumin and bovine γ-globulin at pH 9.2, followed by hydrolysis of the N- or O-acetyl groups at pH 9.5, gave 50% up to 64% yields of the respective conjugates Ig, IIg and Ih, IIh.