Interactions of the Antitumor Agent Molybdocene Dichloride with Oligonucleotides

dc.contributor.authorHarding, Margaret
dc.contributor.authorMokdsi, George
dc.contributor.authorMackay, Joel Peter
dc.contributor.authorProdigalidad, Michael
dc.contributor.authorWright Lucas, Sally
dc.date.accessioned2015-12-13T22:26:21Z
dc.date.issued1998
dc.date.updated2015-12-11T08:21:44Z
dc.description.abstractThe interactions between the antitumor-active metallocene molybdocene dichloride (Cp2MoCl2) and four oligonucleotides have been studied by 1H and 31P NMR spectroscopy. In 50 mM salt solutions of molybdocene dichloride, hydrolysis of the halide ligands occurs to give a solution with pD 2, containing a species in which both Cp rings remain metal bound for 24 h. At pD 7, however, partial hydrolysis of the Cp rings (∼30%) occurs after 24 h. Addition of an aqueous solution of molybdocene dichloride in 50 mM salt to the self-complementary sequence d(CGCATATGCG)2, maintaining the pD at 6.0-7.0, showed no evidence for the formation of a metallocene-oligonucleotide complex, and only peaks arising from hydrolysis of molybdocene dichloride were detected. A similar result was obtained in titration experiments with the single-stranded sequence d(ATGGTA) at pD 6.5-7.0. However, at pD 3.0, new signals assigned to a molybdocene-oligonuleotide complex or complexes were detected in the 1H NMR spectrum. No change was observed in the 31P NMR spectrum. The complex or complexes formed between molybdocene dichloride and d(ATGGTA) are stable for hours at pD 3.0; at higher pD, the complex is destabilized and only peaks arising from hydrolysis of molybdocene dichloride are detected. Titration experiments at low pD with the dinucleotide dCpG showed a new set of signals in the 1H NMR spectrum, tentatively assigned to formation of a complex arising due to coordination of molybdenum to guanine N7 and/or cytosine N3. At pD 7.0, these signals disappeared. The results obtained show that stable oligonucleotide adducts are not formed in 50 mM salt at pD 7.0, and hence it is highly unlikely that formation of molybdocene - DNA adducts in vivo is the primary action that is responsible for the antitumor properties of molybdocene dichloride.
dc.identifier.issn0020-1669
dc.identifier.urihttp://hdl.handle.net/1885/73478
dc.publisherAmerican Chemical Society
dc.sourceInorganic Chemistry
dc.titleInteractions of the Antitumor Agent Molybdocene Dichloride with Oligonucleotides
dc.typeJournal article
local.bibliographicCitation.issue10
local.bibliographicCitation.lastpage2437
local.bibliographicCitation.startpage2432
local.contributor.affiliationHarding, Margaret, Administrative Division, ANU
local.contributor.affiliationMokdsi, George, University of Sydney
local.contributor.affiliationMackay, Joel Peter, University of Sydney
local.contributor.affiliationProdigalidad, Michael, University of Sydney
local.contributor.affiliationWright Lucas, Sally, University of Sydney
local.contributor.authoremailu4044881@anu.edu.au
local.contributor.authoruidHarding, Margaret, u4044881
local.description.embargo2037-12-31
local.description.notesImported from ARIES
local.identifier.absfor030400 - MEDICINAL AND BIOMOLECULAR CHEMISTRY
local.identifier.ariespublicationf5625xPUB3708
local.identifier.citationvolume37
local.identifier.doi10.1021/ic971205k
local.identifier.scopusID2-s2.0-0001340544
local.identifier.uidSubmittedByf5625
local.type.statusPublished Version

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