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New family of rhodium metalloinsertors with improved selectivity and potency against DNA mismatch repair deficient cell lines

Boyle, Kelsey M. and Komor, Alexis and Barton, Jacqueline K. (2015) New family of rhodium metalloinsertors with improved selectivity and potency against DNA mismatch repair deficient cell lines. Abstracts of Papers of the American Chemical Society, 249 . INOR-169. ISSN 0065-7727. https://resolver.caltech.edu/CaltechAUTHORS:20150422-094854656

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Abstract

Rhodium metalloinsertors are a unique family of complexes that selectively bind DNA base pair mismatches. We have seen crystallog. that insertion of the sterically expansive chrysi (5, 6- chrysenequinone diimine) ligand into DNA at a mismatched site leads to the ejection of the mismatched bases. This unique lesion may serve as the biol. target within the cell. Previously, it has been shown that rhodium metalloinsertors preferentially increase cell death and inhibit proliferation of mismatch repair (MMR) - deficient colorectal cancer cell lines over their MMR- proficient counterparts. Recently, a new family of rhodium metalloinsertors contg. a rhodium- oxygen bond has been shown to have improved potency in the nanomolar range as well as increased cytotoxic selectivity toward MMR- deficient cells. This family appears distinct from previous metalloinsertors in that both the Δ- and %λ- isomers of these complexes bind mismatched DNA with similar affinities. Current research is focused on extending the family to include new complexes that will allow us to explain in detail the basis for the high cell selectivity and potency of this new family.


Item Type:Article
Related URLs:
URLURL TypeDescription
http://www.acs.org/content/acs/en/meetings/spring-2015.htmlOrganizationConference Website
ORCID:
AuthorORCID
Boyle, Kelsey M.0000-0002-6728-8403
Barton, Jacqueline K.0000-0001-9883-1600
Additional Information:© 2015 American Chemical Society.
Record Number:CaltechAUTHORS:20150422-094854656
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20150422-094854656
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:56859
Collection:CaltechAUTHORS
Deposited By: Tony Diaz
Deposited On:22 Apr 2015 19:19
Last Modified:03 Oct 2019 08:18

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