Use of Antibodies To Probe the Stereochemistry of Antitumor Platinum Drug Binding to Deoxyribonucleic Acid

Stephen J. Lippard, Carolyn M. Merkel, Stephen J. Lippard, H. Michael Ushay, Miriam C. Poirier, Miriam C. Poirier

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Abstract

A previously prepared antiserum elicited against DNA modified with cis-diamminedichloroplatinum(II) (cis-DDP) (Poirier et al., 1982) was found by a competitive enzyme-linked immunosorbent assay (ELISA) to show high specificity for cis-DDP bound to poly(dG)·poly(dC) but not to the alternating heterocopolymer poly[d(GC)]·poly[d(GC)]. Poor immunoreactivity was shown toward calf thymus DNA modified by a variety of antitumor-inactive platinum analogues including trans-DDP, trans-[Pt(NH2CH3)2Cl2], and [Pt-(dien)Cl]Cl whereas the antiserum exhibited good specificity for DNA modified by analogues having cis stereochemistry. Platinum complexes included in the latter category are [Pt-(en)Cl2], cis-[Pt(NH2CH3)2Cl2], [Pt(CP)(DACH)], and cis-diammineplatinum α-pyridone blue. The ELISA immunoreactivity of cis-DDP-DNA treated with cyanide ion or thiourea after modification or with ethidium bromide during modification was also monitored. Taken together, the results of this study suggest that a primary three-dimensional structure recognized by the antibody is a bidentate adduct of cis-DDP in which two chloride ions have been replaced by two adjacent deoxyguanosines on the same DNA strand.

Original languageEnglish (US)
Pages (from-to)5165-5168
Number of pages4
JournalBiochemistry
Volume22
Issue number22
DOIs
StatePublished - Jan 1 1983

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ASJC Scopus subject areas

  • Biochemistry

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