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Cell-selective activity of rhodium metalloinsertors correlates with subcellular localization

Komor, Alexis C. and Schneider, Curtis J. and Ernst, Russell J. and Weidmann, Alyson G. and Barton, Jacqueline K. (2013) Cell-selective activity of rhodium metalloinsertors correlates with subcellular localization. In: 245th ACS National Meeting & Exposition, Abstracts of Papers, April 7-11, 2013, New Orleans, LA.

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Deficiencies in the mismatch repair (MMR) pathway have been assocd. with various cancers, and many commonly used chemotherapeutics have decreased effectiveness against MMR-deficient cancers. There is consequently a need for chemotherapies that selectively target MMR-deficient cancer cells. Research in our lab. has uncovered a class of compds., rhodium metalloinsertors, that selectively binds to DNA mismatches with high affinity and specificity. These rhodium metalloinsertors bear an expansive arom. chrysi ligand (chrysi= chrysene-5,6-quinonediimine) which, upon mismatch binding, inserts into the DNA duplex from the minor groove and ejects the mismatched bases. These metalloinsertors exhibit selective cytotoxicity, preferentially inducing necrosis in MMR-deficient cells over MMR-proficient cells. They have been found to localize in the nuclei of MMR-deficient cells at concns. sufficient for mismatch detection, and their ability to selectively target MMRdeficient cells has been shown to be contingent upon low mitochondrial rhodium accumulation.

Item Type:Conference or Workshop Item (Paper)
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Barton, Jacqueline K.0000-0001-9883-1600
Additional Information:© 2013 American Chemical Society.
Record Number:CaltechAUTHORS:20130717-152842022
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Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:39424
Deposited By: Tony Diaz
Deposited On:12 Aug 2013 22:40
Last Modified:03 Oct 2019 05:07

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