Synthetic Nucleosides and Nucleotides. XXVII. Selective Inhibition of Deoxyribonucleic Acid Polymerase α by 1-β-D-Arabinofuranosyl-5-styryluracil 5'-Triphosphates and Related Nucleotides : Influence of Hydrophobic and Steric Factors on the Inhibitory Action

抄録

Eight kinds of 5-substituted 1-β-D-arabinofuranosyluracil 5 '-triphosphates ((E) - (3-nitrostyryl) (6), (E) - (3-aminostyryl) (9), (E) - (4-nitrostyryl) (7), (E) - (4-aminostyryl) (10), (E) -styryl (8), phenethyl (11), (RS) - (3-azido-2-hydroxypropyl) (17), and (RS) - (3-amino-2-hydroxypropyl) (18) derivatives) were synthesized. Among these analogs, araUTPs bearing strongly hydrophobic styryl groups at the 5-position (6-10) were shown to have selective and strong inhibitory action on deoxyribonucleic acid (DNA) polymerase α purified from cherry salmon (Oncorhynchus masou) testes. The 5-azidopropyl derivative (17) also inhibited this polymerase. The compounds with a nitro and an amino group on the 5-styryl substituent showed essentially the same activity, but the 5-phenethyl derivative (11) and the 5-aminopropyl derivative (18) showed greatly reduced inhibitory action. On the other hand, in the case of DNA polymerase β, all the analogs showed similar inhibitory effects. The influence of hydrophobic and steric effects of substituents at the 5-position of araUTP on DNA polymerases α and β are discussed.