9-beta-d-arabinofuranosylguanosine-5--triphosphate and Multiple-Myeloma

The effects of the newly synthesized compound 9-beta-D-arabinofuranosylguanine 5'-triphosphate (ara-GTP) on the activity of DNA polymerases from mouse cells and oncornavirus were compared with those of 9-beta-D-arabinofuranosyladenine 5'-triphosphate. Ara-GTP did not replace deoxyguanosine 5'- triphosphate as substrate for these DNA polymerases but inhibited the activities of DNA polymerase alpha, beta, and gamma and viral DNA polymerase. DNA polymerase alpha was more sensitive than DNA polymerases beta and gamma and viral DNA polymerase to inhibition by ara-GTP. The inhibitions by ara-GTP and 9-beta-D-arabinofuranosyladenine 5'-triphosphate were due to competition or partial competition 5'-triphosphate were due to competition or partial competition with deoxynucleoside triphosphate with the same base. The inhibition constant (Ki) and the mode of inhibition of nucleotide incorporation varied depending on the combination of inhibitor, substrate(s), and enzyme species.

Topics: Animals; Arabinonucleotides; Cells, Cultured; Deoxyribonucleotides; Guanosine Triphosphate; Kinetics; Mice; Multiple Myeloma; Neoplasms, Experimental; Nucleic Acid Synthesis Inhibitors; Rats; Rauscher Virus; Substrate Specificity; Vidarabine Phosphate