Interaction of the Antitumor Agents cis,cis,trans-PtIV(NH3)2Cl2(OH)2 and cis,cis,trans-PtIV[(CH3)2CHNH2]2Cl2(OH)2 and Their Reduction Products with PM2 DNA

Erich E. Blatter; Jean F. Vollano; James C. Dabrowiak; Bala S. Krishnan

doi:10.1021/bi00316a001

Interaction of the Antitumor Agents cis,cis,trans-Pt^IV(NH₃)₂Cl₂(OH)₂ and cis,cis,trans-Pt^IV[(CH₃)₂CHNH₂]₂Cl₂(OH)₂ and Their Reduction Products with PM2 DNA

Erich E. Blatter, Jean F. Vollano, James C. Dabrowiak, Bala S. Krishnan

Department of Chemistry

Research output: Contribution to journal › Article › peer-review

113 Scopus citations

Abstract

The ability of two platinum(IV) antitumor agents, cis,cis,trans-Pt^IV[(CH₃)₂CHNH₂]₂Cl₂(OH)₂ (2) and cis,-cis,tranS-Pt^IV(NH₃)₂Cl₂OH)₂ (4), to interact with PM2 DNA was examined. Analysis using gel electrophoresis showed that neither compound is able to alter the electrophoretic mobihties of the three forms of PM2 DNA in the gel. However, incubation of 2 and 4 with 2 equiv of Fe(ClO₄)₂·6H₂O or 1 equiv of ascorbic acid results in reduction to yield the divalent complexes m-Pt^II(NH₃)₂Cl₂ (1) and cis-Pt^II-[(CH₃)₂CHNH₂]₂C1₂ (3). The structures of the reduction products were characterized by using elemental analysis as well as infrared and ¹⁹⁵Pt NMR spectroscopies. Both 1 and 3 were found to bind to and unwind supercoiled form I PM2 DNA. The aforementioned observations support the suggestion that reduction is a means of activating the antitumor properties of 2 and 4.

Original language	English (US)
Pages (from-to)	4817-4820
Number of pages	4
Journal	Biochemistry
Volume	23
Issue number	21
DOIs	https://doi.org/10.1021/bi00316a001
State	Published - Oct 1984

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Biochemistry

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@article{625a86cae49745758e6b94cb87461ae9,

title = "Interaction of the Antitumor Agents cis,cis,trans-PtIV(NH3)2Cl2(OH)2 and cis,cis,trans-PtIV[(CH3)2CHNH2]2Cl2(OH)2 and Their Reduction Products with PM2 DNA",

abstract = "The ability of two platinum(IV) antitumor agents, cis,cis,trans-PtIV[(CH3)2CHNH2]2Cl2(OH)2 (2) and cis,-cis,tranS-PtIV(NH3)2Cl2OH)2 (4), to interact with PM2 DNA was examined. Analysis using gel electrophoresis showed that neither compound is able to alter the electrophoretic mobihties of the three forms of PM2 DNA in the gel. However, incubation of 2 and 4 with 2 equiv of Fe(ClO4)2·6H2O or 1 equiv of ascorbic acid results in reduction to yield the divalent complexes m-PtII(NH3)2Cl2 (1) and cis-PtII-[(CH3)2CHNH2]2C12 (3). The structures of the reduction products were characterized by using elemental analysis as well as infrared and 195Pt NMR spectroscopies. Both 1 and 3 were found to bind to and unwind supercoiled form I PM2 DNA. The aforementioned observations support the suggestion that reduction is a means of activating the antitumor properties of 2 and 4.",

author = "Blatter, {Erich E.} and Vollano, {Jean F.} and Dabrowiak, {James C.} and Krishnan, {Bala S.}",

year = "1984",

month = oct,

doi = "10.1021/bi00316a001",

language = "English (US)",

volume = "23",

pages = "4817--4820",

journal = "Biochemistry",

issn = "0006-2960",

publisher = "American Chemical Society",

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TY - JOUR

T1 - Interaction of the Antitumor Agents cis,cis,trans-PtIV(NH3)2Cl2(OH)2 and cis,cis,trans-PtIV[(CH3)2CHNH2]2Cl2(OH)2 and Their Reduction Products with PM2 DNA

AU - Blatter, Erich E.

AU - Vollano, Jean F.

AU - Dabrowiak, James C.

AU - Krishnan, Bala S.

PY - 1984/10

Y1 - 1984/10

N2 - The ability of two platinum(IV) antitumor agents, cis,cis,trans-PtIV[(CH3)2CHNH2]2Cl2(OH)2 (2) and cis,-cis,tranS-PtIV(NH3)2Cl2OH)2 (4), to interact with PM2 DNA was examined. Analysis using gel electrophoresis showed that neither compound is able to alter the electrophoretic mobihties of the three forms of PM2 DNA in the gel. However, incubation of 2 and 4 with 2 equiv of Fe(ClO4)2·6H2O or 1 equiv of ascorbic acid results in reduction to yield the divalent complexes m-PtII(NH3)2Cl2 (1) and cis-PtII-[(CH3)2CHNH2]2C12 (3). The structures of the reduction products were characterized by using elemental analysis as well as infrared and 195Pt NMR spectroscopies. Both 1 and 3 were found to bind to and unwind supercoiled form I PM2 DNA. The aforementioned observations support the suggestion that reduction is a means of activating the antitumor properties of 2 and 4.

AB - The ability of two platinum(IV) antitumor agents, cis,cis,trans-PtIV[(CH3)2CHNH2]2Cl2(OH)2 (2) and cis,-cis,tranS-PtIV(NH3)2Cl2OH)2 (4), to interact with PM2 DNA was examined. Analysis using gel electrophoresis showed that neither compound is able to alter the electrophoretic mobihties of the three forms of PM2 DNA in the gel. However, incubation of 2 and 4 with 2 equiv of Fe(ClO4)2·6H2O or 1 equiv of ascorbic acid results in reduction to yield the divalent complexes m-PtII(NH3)2Cl2 (1) and cis-PtII-[(CH3)2CHNH2]2C12 (3). The structures of the reduction products were characterized by using elemental analysis as well as infrared and 195Pt NMR spectroscopies. Both 1 and 3 were found to bind to and unwind supercoiled form I PM2 DNA. The aforementioned observations support the suggestion that reduction is a means of activating the antitumor properties of 2 and 4.

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JO - Biochemistry

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Interaction of the Antitumor Agents cis,cis,trans-Pt^IV(NH₃)₂Cl₂(OH)₂ and cis,cis,trans-Pt^IV[(CH₃)₂CHNH₂]₂Cl₂(OH)₂ and Their Reduction Products with PM2 DNA

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