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Development of rhodium metalloinsertors as chemotherapeutic agents

Komor, Alexis and Barton, Jacqueline K. (2015) Development of rhodium metalloinsertors as chemotherapeutic agents. Abstracts of Papers of the American Chemical Society, 249 . INOR-793. ISSN 0065-7727.

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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. Rhodium metalloinsertors are octahedral complexes that bind DNA mismatches with high affinity and specificity through metalloinsertion, a binding mode through which the compds. insert into the DNA duplex from the minor groove and eject the mismatched bases. These compds. also exhibit unique cell- selective cytotoxicity, preferentially inducing necrosis in mismatch repair (MMR) - deficient cells over MMR- proficient cells. This chemotherapeutic activity, which has been confirmed across multiple assays and in different systems for comparing MMR deficiency to proficiency, has been found to be the result of specific targeting of the metalloinsertors to nuclear DNA mismatches. Most recently, a new generation of metalloinsertors with enhanced potency and selectivity has been discovered which display Rh- O coordination and a possible different binding disposition in the mismatch site as compared to earlier generation metalloinsertors.

Item Type:Article
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Barton, Jacqueline K.0000-0001-9883-1600
Additional Information:© 2015 American Chemical Society.
Record Number:CaltechAUTHORS:20150414-131045800
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Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:56637
Deposited By: Tony Diaz
Deposited On:15 Apr 2015 04:34
Last Modified:03 Oct 2019 08:15

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