SUBSTRATE-SPECIFICITY OF GLYCINAMIDE RIBONUCLEOTIDE TRANSFORMYLASE FROM CHICKEN LIVER

Several glycinamide ribonucleotide analogs have been prepared and eval uated as substrates and/or inhibitors of glycinamide ribonucleotide tr ansformylase from chicken liver. The side chain modified analogs, in w hich the glycine side chain, R = CH2NH2, has been replaced by R = CH2N HCH3 and R = CH2CH2NH2, are substrates, with V/K (relative intensity) of 2.4% and 16.3%, respectively. Several carbocyclic analogs of glycin amide ribonucleotide, including the phosphonate derivative of carbocyc lic glycinamide ribonucleotide, did not serve as substrates, but were inhibitors of the enzyme, competitive against glycinamide ribonucleoti de, with K-i values ranging from 7.4 to 23.6 times the K-m for glycina mide ribonucleotide. However, the O-phosphonate analog of carbocyclic glycinamide ribonucleotide did support enzymatic activity, with V/K (r elative intensity) of 0.8%. In addition, glycinamide ribonucleoside wa s neither a substrate for, nor an inhibitor of, glycinamide ribonucleo tide transformylase. Furthermore, alpha-glycinamide ribonucleotide had no effect on enzyme activity. These studies have begun to define the structural features of the nucleotide substrate required to support en zymatic activity.