Collect. Czech. Chem. Commun. 1979, 44, 1634-1641

Synthesis of conjugates of 5-halouracils with proteins using activated esters

Helmut Pischela, Antonín Holýb and Günther Wagnera

a Sektion Biowissenschaften-Pharmazie, Karl-Marx-Universitat, Leipzig, G.D.R.
b Institute of Organic Chemistry and Biochemistry, Czechoslovak Academy of Sciences, 166 10 Prague 6, Czechoslovakia


1-Carboxymethyluracil (Ia) and its 5-fluoro (Ib), 5-bromo (Ic) and 5-iodo (Id) derivatives were transformed into the p-nitrophenyl esters IIa-IId by reaction with p-nitrophenol in the presence of N,N'-dicyclohexylcarbodiimide. Reaction of these compounds with ammonia or ε-aminocaproic acid afforded the corresponding 1-aminocarbonylmethyluracil (IIIa-d) and 1-N-(5-carboxypentyl)aminocarbonylmethyluracil (IVa-d) derivatives. Reaction of compounds II with human serum albumin and bovine γ-globulin at pH 9.2 gave high yields of conjugates of the type V and VI, respectively, containing 10-50 uracil derivative moieties bound to the protein molecule.