SYNTHESIS OF WATER-SOLUBLE BILE-PIGMENTS BOUND TO AMINE-ENDED MONOMETHOXYPOLYETHYLENEGLYCOL - THIOL ADDITION AND ATTEMPTED ENZYMATIC REDUCTION OF A BILINDIONE DERIVATIVE

The water-soluble amide to an NH2-ended monomethoxypolyethyleneglycol (MPEG-NH2, molecular mass of about 2000) of the dipyrrinone xanthobili rubic acid (XBR, 1) and the bis-amides of mesobiliverdiu-XIII alpha (M BV, 2) and mesobilirubin-XIII alpha (MBR, 3) have been prepared with h igh yields. Contrary to what is observed with biliverdin-IX alpha, 4, the enzymatic reduction of the mesobiliverdin derivative 2-MPEGA to th e corresponding mesobilirubin 3-MPEGA by the soluble biliverdin reduct ase/NADPH system in pH 7.4 aqueous phosphate does not occur. In contra st, thiol addition to 2-MPEGA and to 4 under similar conditions is imm ediate, although this equilibrium is slightly less favourable for 2-MP EGA. These results enable us to discount the intrinsically low reactiv ity of 2-MPEGA towards thiols as the reason for its lack of enzymatic reduction, and suggest instead that this particular mesobiliverdin can not fit properly into the enzyme binding site, either because of steri c hindrance or the lack of the two propionic acid groups.