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...
Autores principales: | , , , , , , |
---|---|
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 |