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Construction and Application of a Rh–Pt DNA Metalloinsertor Conjugate

Weidmann, Alyson G. and Barton, Jacqueline K. (2014) Construction and Application of a Rh–Pt DNA Metalloinsertor Conjugate. Inorganic Chemistry, 53 (15). pp. 7812-7814. ISSN 0020-1669. PMCID PMC4123934. doi:10.1021/ic501509x.

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We report the synthesis and characterization of a bimetallic conjugate (RhPt) in which an oxaliplatin derivative is tethered to a rhodium metalloinsertor through an aminomalonate leaving group ligand. The complex interacts with DNA through metalloinsertion at a base pair mismatch followed by formation of a covalent Pt–DNA adduct. Characterization of RhPt in mismatch repair-deficient HCT116O cells reveals increased cytotoxicity compared to cisplatin and oxaliplatin as well as relative to the unconjugated rhodium and platinum counterparts. Caspase and poly-ADP ribose polymerase inhibition assays indicate that RhPt induces apoptotic cell death. Inductively coupled plasma mass spectrometry (ICP-MS) experiments reveal that RhPt exhibits enhanced cellular uptake properties that contribute to its increased efficacy.

Item Type:Article
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Barton, Jacqueline K.0000-0001-9883-1600
Additional Information:© 2014 American Chemical Society. ACS AuthorChoice. Received: June 24, 2014. Publication Date (Web): July 17, 2014. We are grateful for instrumentation made available by the Caltech Environmental Analysis Center.
Issue or Number:15
PubMed Central ID:PMC4123934
Record Number:CaltechAUTHORS:20140721-085331031
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Official Citation:Construction and Application of a Rh–Pt DNA Metalloinsertor Conjugate Alyson G. Weidmann and Jacqueline K. Barton Inorganic Chemistry 2014 53 (15), 7812-7814
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:47355
Deposited By: Tony Diaz
Deposited On:21 Jul 2014 19:13
Last Modified:10 Nov 2021 17:38

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