The interaction of transition metal-based anticancer compounds with nucleic acids

Eberle, Rahel Patricia; Schürch, Stefan (26 October 2017). The interaction of transition metal-based anticancer compounds with nucleic acids (Unpublished). In: Swiss Group for Mass Spectrometry, 2017 Annual Meeting. Beatenberg, Switzerland. October 25-27, 2017.

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

The discovery of the antitumor activity of cisplatin represented a milestone in the transition metal-based chemotherapy. Despite the great success of cisplatin against a variety of cancer types, severe side effects and resistances (aquired or intrinsic) necessitated the development of alternative anticancer agents. Metallocene dichlorides (Cp2MCl2, with Cp=cyclopentadienyl, M=Ti, V, Nb, Mo) and their derivatives are a class of metallodrugs with promising anticancer characteristics. Their activity against cisplatin-resistant cell lines combined with their general low toxicity motivated the synthesis of novel Cp-functionalized metallocenes. The antitumor activity of certain metallocenes (e.g., titanocene) is reported to arise from the interaction with nuclear DNA. However, the precise mechanisms of action are not fully elucidated yet and appear to be rather diverse. Building on previous ESI-MS/MS experiments with dinucleoside monophosphates, this study investigates the binding preferences and binding sites of titanocene with DNA and RNA hexanucelotides. The influence of the sugar moiety, the types of nucleobases, and the nucleobase sequences on the adduct formation was elucidated by means of competition experiments. To localize the exact binding sites in MS/MS experiments, the precursors were dissociated by different activation techniques (CID, HCD, and ETD). The effect of the titanium coordination center on the gas-phase dissociation of the nucleic acids is discussed.

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 > 570 Life sciences; biology
500 Science > 540 Chemistry
600 Technology > 610 Medicine & health

Funders:

[4] Swiss National Science Foundation

Language:

English

Submitter:

Stefan Schürch

Date Deposited:

13 Apr 2018 15:25

Last Modified:

13 Apr 2018 15:25

URI:

https://boris.unibe.ch/id/eprint/113513

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