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Synthesis and characterization of a heterobimetallic Rh(III)/Pt(II) metalloinsertor conjugate

Weidmann, Alyson G. and Komor, Alexis C. and Schneider, Curtis J. and Barton, Jacqueline K. (2014) Synthesis and characterization of a heterobimetallic Rh(III)/Pt(II) metalloinsertor conjugate. In: 247th ACS National Meeting & Exposition, March 16-20, 2014, Dallas, TX.

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Deficiencies in the mismatch repair (MMR) machinery lead to DNA defects that cause cancer. Cancers that exhibit MMR deficiency are typically resistant to cisplatin and carboplatin, but can be treated in part with oxaliplatin. Recently, we have shown that rhodium metalloinsertors, which bind DNA at mismatched sites with over 1000 fold selectivity, exhibit antiproliferative and cytotoxic activity selectively in cells that are MMR-deficient. A bimetallic complex, consisting of a rhodium metalloinsertor tethered to an oxaliplatin deriv., was synthesized to improve platinum efficacy in an MMR-deficient human colorectal carcinoma line (HCT116O). The addn. of the rhodium metalloinsertor significantly increases cytotoxic activity and whole-cell platinum uptake compared to that of unconjugated platinum, as well as cisplatin and oxaliplatin. DNA binding studies show that the complex interacts with DNA through both metalloinsertion at a mismatch as well as the formation of Pt-DNA crosslinks.

Item Type:Conference or Workshop Item (Paper)
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Barton, Jacqueline K.0000-0001-9883-1600
Additional Information:© 2014 American Chemical Society.
Record Number:CaltechAUTHORS:20140506-142144076
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Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:45539
Deposited By: Tony Diaz
Deposited On:06 May 2014 23:17
Last Modified:03 Oct 2019 06:32

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