Base1 (8.IX.80) Nucleosides and Nucleotides. Part 16. The Behaviour of 1-(2'-Deoxy-~-D-ribofurauosyl-2(1H)pyrimidinone-5'-triphosphate, 1~2'-Deoxy-~-~-ribofuranosyI-2(lH)-pyridinone-5'-triphosphate and 4-Amino-I -(2'-deoxy-~-~-ribofuranosyl)-2(1H)-pyridinone-5'-triphosphate towards DNA Polymerase
Summary
The behaviour of nucleotide base analogs in the DNA synthesis in vitro was studied. The investigated nucleoside-5'-triphosphates 1-(2'-deoxy-/3-~-ribofUranosyl)-2( 1 H)-pyrimidinone-5'-triphosphate (pppM,),
1-(2'-deoxy-/3-~-ribofuranosyl)-2(1 H)-pyridinone-.5'-triphosphate (pppl7,) and 4-amino-1-(2'-deoxy-P-~-ribo-furanosy1)-2( 1 H)-pyridinone-5'-triphosphate (pppz,) can be considered to be analogs of 2'-deoxy-cytidine-5'-triphosphate. However, their ability to undergo base pairing to the complementary guanine is decreased. When pppM,, pppnd or PPPZd are substituted for PPPCd in the enzymatic synthesis of DNA by DNA polymerase no incorporation of these analogs is observed. They exhibit only a weak inhibition of the DNA synthesis. The mode of the inhibition is uncompetitive which shows that these nucleotide analogs cannot serve as substrates for the DNA polymerase. 1. Einleitung. -Tm Jahre 1958 haben Bessman et al. [2] zum ersten Ma1 gezeigt, dass es moglich ist, bestimmte Nucleotid-Analoga, deren Basen modifiziert sind, in eine Desoxyribonucleinsaure (DNA) mit Hilfe der DNA-Polymerase einzubauen. Dabei ist die Art der Modifikation von entscheidender Bedeutung. Bestimmte Strukturveranderungen der Base an Stellen, die an der Ausbildung der Wasserstoffbrucken gemass dem Watson-Crick Model1 [3] nicht beteiligt sind,