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Targeting DNA mismatches with rhodium metalloinsertors

Boyle, Kelsey M. and Barton, Jacqueline K. (2016) Targeting DNA mismatches with rhodium metalloinsertors. Inorganica Chimica Acta, 452 . pp. 3-11. ISSN 0020-1693. PMCID PMC5061454. doi:10.1016/j.ica.2016.01.021. https://resolver.caltech.edu/CaltechAUTHORS:20160125-103800513

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Abstract

DNA has been exploited as a biological target of chemotherapeutics since the 1940s. Traditional chemotherapeutics, such as cisplatin and DNA-alkylating agents, rely primarily on increased uptake by rapidly proliferating cancer cells for therapeutic effects, but this strategy can result in off-target toxicity in healthy tissue. Recently, research interests have shifted towards targeted chemotherapeutics, in which a drug targets a specific biological signature of cancer, resulting in selective toxicity towards cancerous cells. Here, we review a family of complexes, termed rhodium metalloinsertors, that selectively target DNA base pair mismatches, a hallmark of mismatch repair (MMR)-deficient cancers. These rhodium metalloinsertors bind DNA mismatches with high specificity and display high selectively in killing MMR-deficient versus MMR-proficient cells. This cell selectivity is unique among small molecules that bind DNA. Current generations of rhodium metalloinsertors have shown nanomolar potency along with high selectivity towards MMR-deficient cells, and show promise as a foundation for a new family of chemotherapeutics for MMR-deficient cancers.


Item Type:Article
Related URLs:
URLURL TypeDescription
https://doi.org/10.1016/j.ica.2016.01.021DOIArticle
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5061454PubMed CentralArticle
ORCID:
AuthorORCID
Boyle, Kelsey M.0000-0002-6728-8403
Barton, Jacqueline K.0000-0001-9883-1600
Additional Information:© 2016 Published by Elsevier B.V. Received 30 November 2015; Received in revised form 7 January 2016; Accepted 11 January 2016. We are grateful to our coworkers and collaborators in elucidating this chemistry and to the NIH for their support of this research (GM33309). We also thank the United States Department of Defense for an NDSEG research fellowship to K.M.B.
Funders:
Funding AgencyGrant Number
NIHGM33309
National Defense Science and Engineering Graduate (NDSEG) FellowshipUNSPECIFIED
Subject Keywords:Rhodium; Metalloinsertor; Mismatch repair; DNA probe
PubMed Central ID:PMC5061454
DOI:10.1016/j.ica.2016.01.021
Record Number:CaltechAUTHORS:20160125-103800513
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20160125-103800513
Official Citation:Kelsey M. Boyle, Jacqueline K. Barton, Targeting DNA mismatches with rhodium metalloinsertors, Inorganica Chimica Acta, Volume 452, 1 October 2016, Pages 3-11, ISSN 0020-1693, http://dx.doi.org/10.1016/j.ica.2016.01.021. (http://www.sciencedirect.com/science/article/pii/S0020169316000323)
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:63926
Collection:CaltechAUTHORS
Deposited By: Tony Diaz
Deposited On:25 Jan 2016 19:19
Last Modified:10 Nov 2021 23:23

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