Binding of Metallocenes to Short Oligonucleotides

Eberle, Rahel Patricia; Schürch, Stefan (4 September 2015). Binding of Metallocenes to Short Oligonucleotides (Unpublished). In: SCS Fall Meeting. Lausanne. 04.09.2015.

Official URL: http://www.scg.ch

Cancer is one of the most severe and widespread diseases and an ideal treatment has not yet been found. In the last decades, cisplatinum was commonly applied in cancer therapy with very good results. However, serious side effects and resistant tumors necessitated the development of new antineoplastic agents, such as metallocenes dihalides. These are metal-based compounds exhibiting two cyclopentadienyl ligands and a cis-dihalide motif. They resemble the cis-chloro configuration of cisplatinum, which propounds a similar mode of action. Metallocenes comprising one of the transition metals titanium, molybdenum, vanadium, niobium, and zirconium as the metal center have been shown to be effective against several cancer cell lines. Evidence for the accumulation of metallocenes in the nucleus implied that DNA is one of the major targets. Although several studies reported adduct formation of metallocenes with nuclear DNA, as yet substantial information about the general binding pattern and the binding to higher-order structures is lacking. Mass spectrometry can fill this gap as it constitutes a powerful technique to investigate the formation of organometallic adducts. Presented data demonstrate that the two agents titanocene dichloride and molybdenocene dichloride bind to single-stranded DNA and RNA. Distinct fragment ions formed upon collision-induced dissociation help to unravel preferential binding sites within the oligonucleotides. Moreover, adducts with duplexes and quadruplexes shed light on the molecular mechanism of action.

Item Type:

Conference or Workshop Item (Poster)

Division/Institute:

08 Faculty of Science > Departement of Chemistry and Biochemistry

UniBE Contributor:

Eberle, Rahel Patricia and Schürch, Stefan

Subjects:

500 Science > 540 Chemistry
600 Technology > 610 Medicine & health

Language:

English

Submitter:

Stefan Schürch

Date Deposited:

02 Feb 2016 15:54

Last Modified:

02 Feb 2016 15:54

URI:

https://boris.unibe.ch/id/eprint/75104

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