Cargando…

Sequence‐dependent Termination of Mammalian DNA Polymerase Reaction by a New Platinum Compound, (–)‐(R)‐2‐Aminomethylpyrrolidine(1,1‐cyclobutane‐dicarboxylato)‐2‐platinum(II) Monohydrate

We examined the mechanisms of the inhibition of DNA synthesis by a new platinum compound, (‐)‐(R)‐2‐aminomethylpyrrolidine(1,1‐cyclobutane‐dicarboxylato)‐2‐platinum(II) monohydrate (DWA‐2114R), a derivative of the antitumor drug cis‐ diamminedichloroplatinum(II) (CDDP), using prokaryotic and eukaryo...

Descripción completa

Detalles Bibliográficos
Autores principales: Iwata, Mitsumasa, Izuta, Shunji, Suzuki, Motoshi, Kojima, Kiyohide, Furuhashi, Yoshihito, Tomoda, Yutaka, Yoshida, Shonen
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Blackwell Publishing Ltd 1991
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5918450/
https://www.ncbi.nlm.nih.gov/pubmed/1904423
http://dx.doi.org/10.1111/j.1349-7006.1991.tb01867.x
_version_ 1783317418967302144
author Iwata, Mitsumasa
Izuta, Shunji
Suzuki, Motoshi
Kojima, Kiyohide
Furuhashi, Yoshihito
Tomoda, Yutaka
Yoshida, Shonen
author_facet Iwata, Mitsumasa
Izuta, Shunji
Suzuki, Motoshi
Kojima, Kiyohide
Furuhashi, Yoshihito
Tomoda, Yutaka
Yoshida, Shonen
author_sort Iwata, Mitsumasa
collection PubMed
description We examined the mechanisms of the inhibition of DNA synthesis by a new platinum compound, (‐)‐(R)‐2‐aminomethylpyrrolidine(1,1‐cyclobutane‐dicarboxylato)‐2‐platinum(II) monohydrate (DWA‐2114R), a derivative of the antitumor drug cis‐ diamminedichloroplatinum(II) (CDDP), using prokaryotic and eukaryotic DNA polymerases. Preincubating activated DNA with CDDP or DWA‐2114R reduced its template activity for prokaryotic and eukaryotic DNA polymerases in a dose‐dependent manner. DWA2114R required six times greater drug concentration and two times longer incubation time to show the same decrease of the template activity compared to CDDP. Treatment of primed pUC118 ssDNA templates with the two drugs followed by second‐strand synthesis by prokaryotic and eukaryotic DNA polymerases revealed that DWA2114R bound to DNA in a similar manner to CDDP and these adducts blocked DNA elongation by DNA polymerases of eukaryotes as well as of prokaryotes. With these two drugs, the elongations by E. coli DNA polymerase I (Klenow fragment), T7 DNA polymerase and calf thymus DNA polymerase α were strongly arrested at guanine‐guanine sequences (GG). Stop bands were also observed at adenine‐guanine sequences (AG) guanine‐adenine‐guanine sequences (GAG) and mono‐guanine sequence (G). Calf testis DNA polymerase β was also arrested efficiently at AG, GAG and G, but much more weakly at GG. This pattern was common to DWA2114R and CDDP.
format Online
Article
Text
id pubmed-5918450
institution National Center for Biotechnology Information
language English
publishDate 1991
publisher Blackwell Publishing Ltd
record_format MEDLINE/PubMed
spelling pubmed-59184502018-05-11 Sequence‐dependent Termination of Mammalian DNA Polymerase Reaction by a New Platinum Compound, (–)‐(R)‐2‐Aminomethylpyrrolidine(1,1‐cyclobutane‐dicarboxylato)‐2‐platinum(II) Monohydrate Iwata, Mitsumasa Izuta, Shunji Suzuki, Motoshi Kojima, Kiyohide Furuhashi, Yoshihito Tomoda, Yutaka Yoshida, Shonen Jpn J Cancer Res Article We examined the mechanisms of the inhibition of DNA synthesis by a new platinum compound, (‐)‐(R)‐2‐aminomethylpyrrolidine(1,1‐cyclobutane‐dicarboxylato)‐2‐platinum(II) monohydrate (DWA‐2114R), a derivative of the antitumor drug cis‐ diamminedichloroplatinum(II) (CDDP), using prokaryotic and eukaryotic DNA polymerases. Preincubating activated DNA with CDDP or DWA‐2114R reduced its template activity for prokaryotic and eukaryotic DNA polymerases in a dose‐dependent manner. DWA2114R required six times greater drug concentration and two times longer incubation time to show the same decrease of the template activity compared to CDDP. Treatment of primed pUC118 ssDNA templates with the two drugs followed by second‐strand synthesis by prokaryotic and eukaryotic DNA polymerases revealed that DWA2114R bound to DNA in a similar manner to CDDP and these adducts blocked DNA elongation by DNA polymerases of eukaryotes as well as of prokaryotes. With these two drugs, the elongations by E. coli DNA polymerase I (Klenow fragment), T7 DNA polymerase and calf thymus DNA polymerase α were strongly arrested at guanine‐guanine sequences (GG). Stop bands were also observed at adenine‐guanine sequences (AG) guanine‐adenine‐guanine sequences (GAG) and mono‐guanine sequence (G). Calf testis DNA polymerase β was also arrested efficiently at AG, GAG and G, but much more weakly at GG. This pattern was common to DWA2114R and CDDP. Blackwell Publishing Ltd 1991-04 /pmc/articles/PMC5918450/ /pubmed/1904423 http://dx.doi.org/10.1111/j.1349-7006.1991.tb01867.x Text en
spellingShingle Article
Iwata, Mitsumasa
Izuta, Shunji
Suzuki, Motoshi
Kojima, Kiyohide
Furuhashi, Yoshihito
Tomoda, Yutaka
Yoshida, Shonen
Sequence‐dependent Termination of Mammalian DNA Polymerase Reaction by a New Platinum Compound, (–)‐(R)‐2‐Aminomethylpyrrolidine(1,1‐cyclobutane‐dicarboxylato)‐2‐platinum(II) Monohydrate
title Sequence‐dependent Termination of Mammalian DNA Polymerase Reaction by a New Platinum Compound, (–)‐(R)‐2‐Aminomethylpyrrolidine(1,1‐cyclobutane‐dicarboxylato)‐2‐platinum(II) Monohydrate
title_full Sequence‐dependent Termination of Mammalian DNA Polymerase Reaction by a New Platinum Compound, (–)‐(R)‐2‐Aminomethylpyrrolidine(1,1‐cyclobutane‐dicarboxylato)‐2‐platinum(II) Monohydrate
title_fullStr Sequence‐dependent Termination of Mammalian DNA Polymerase Reaction by a New Platinum Compound, (–)‐(R)‐2‐Aminomethylpyrrolidine(1,1‐cyclobutane‐dicarboxylato)‐2‐platinum(II) Monohydrate
title_full_unstemmed Sequence‐dependent Termination of Mammalian DNA Polymerase Reaction by a New Platinum Compound, (–)‐(R)‐2‐Aminomethylpyrrolidine(1,1‐cyclobutane‐dicarboxylato)‐2‐platinum(II) Monohydrate
title_short Sequence‐dependent Termination of Mammalian DNA Polymerase Reaction by a New Platinum Compound, (–)‐(R)‐2‐Aminomethylpyrrolidine(1,1‐cyclobutane‐dicarboxylato)‐2‐platinum(II) Monohydrate
title_sort sequence‐dependent termination of mammalian dna polymerase reaction by a new platinum compound, (–)‐(r)‐2‐aminomethylpyrrolidine(1,1‐cyclobutane‐dicarboxylato)‐2‐platinum(ii) monohydrate
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5918450/
https://www.ncbi.nlm.nih.gov/pubmed/1904423
http://dx.doi.org/10.1111/j.1349-7006.1991.tb01867.x
work_keys_str_mv AT iwatamitsumasa sequencedependentterminationofmammaliandnapolymerasereactionbyanewplatinumcompoundr2aminomethylpyrrolidine11cyclobutanedicarboxylato2platinumiimonohydrate
AT izutashunji sequencedependentterminationofmammaliandnapolymerasereactionbyanewplatinumcompoundr2aminomethylpyrrolidine11cyclobutanedicarboxylato2platinumiimonohydrate
AT suzukimotoshi sequencedependentterminationofmammaliandnapolymerasereactionbyanewplatinumcompoundr2aminomethylpyrrolidine11cyclobutanedicarboxylato2platinumiimonohydrate
AT kojimakiyohide sequencedependentterminationofmammaliandnapolymerasereactionbyanewplatinumcompoundr2aminomethylpyrrolidine11cyclobutanedicarboxylato2platinumiimonohydrate
AT furuhashiyoshihito sequencedependentterminationofmammaliandnapolymerasereactionbyanewplatinumcompoundr2aminomethylpyrrolidine11cyclobutanedicarboxylato2platinumiimonohydrate
AT tomodayutaka sequencedependentterminationofmammaliandnapolymerasereactionbyanewplatinumcompoundr2aminomethylpyrrolidine11cyclobutanedicarboxylato2platinumiimonohydrate
AT yoshidashonen sequencedependentterminationofmammaliandnapolymerasereactionbyanewplatinumcompoundr2aminomethylpyrrolidine11cyclobutanedicarboxylato2platinumiimonohydrate