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[Ru(Me_4phen)_2dppz]^(2+), a Light Switch for DNA Mismatches

Boynton, Adam N. and Marcélis, Lionel and Barton, Jacqueline K. (2016) [Ru(Me_4phen)_2dppz]^(2+), a Light Switch for DNA Mismatches. Journal of the American Chemical Society, 138 (15). pp. 5020-5023. ISSN 0002-7863. PMCID PMC4989906. doi:10.1021/jacs.6b02022. https://resolver.caltech.edu/CaltechAUTHORS:20160418-100658436

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Abstract

[Ru(Me_4phen)_2dppz]^(2+) serves as a luminescent “light switch” for single base mismatches in DNA. The preferential luminescence enhancement observed with mismatches results from two factors: (i) the complex possesses a 26-fold higher binding affinity toward the mismatch compared to well-matched base pairs, and (ii) the excited state emission lifetime of the ruthenium bound to the DNA mismatch is 160 ns versus 35 ns when bound to a matched site. Results indicate that the complex binds to the mismatch through a metalloinsertion binding mode. Cu(phen)_2^(2+) quenching experiments show that the complex binds to the mismatch from the minor groove, characteristic of metalloinsertion. Additionally, the luminescence intensity of the complex with DNA containing single base mismatches correlates with the thermodynamic destabilization of the mismatch, also consistent with binding through metalloinsertion. This complex represents a potentially new early cancer diagnostic for detecting deficiencies in mismatch repair.


Item Type:Article
Related URLs:
URLURL TypeDescription
http://dx.doi.org/10.1021/jacs.6b02022DOIArticle
http://pubs.acs.org/doi/suppl/10.1021/jacs.6b02022PublisherSupporting Information
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4989906PubMed CentralArticle
ORCID:
AuthorORCID
Boynton, Adam N.0000-0003-4427-513X
Marcélis, Lionel0000-0002-6324-477X
Barton, Jacqueline K.0000-0001-9883-1600
Alternate Title:[Ru(Me4phen)2dppz]2+, a Light Switch for DNA Mismatches
Additional Information:© 2016 American Chemical Society. Received: February 23, 2016. Publication Date (Web): April 12, 2016. We are grateful to the NIH (GM033309) for funding this work. L.M. thanks the Belgian American Educational Foundation for the Cabeaux−Jacobs Fellowship. We also thank Sarah Antilla for assisting in studies of the complex. The authors declare no competing financial interest.
Funders:
Funding AgencyGrant Number
NIHGM033309
Belgian American Educational FoundationUNSPECIFIED
Issue or Number:15
PubMed Central ID:PMC4989906
DOI:10.1021/jacs.6b02022
Record Number:CaltechAUTHORS:20160418-100658436
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20160418-100658436
Official Citation:[Ru(Me4phen)2dppz]2+, a Light Switch for DNA Mismatches Adam N. Boynton, Lionel Marcélis, and Jacqueline K. Barton Journal of the American Chemical Society 2016 138 (15), 5020-5023 DOI: 10.1021/jacs.6b02022
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:66238
Collection:CaltechAUTHORS
Deposited By: Tony Diaz
Deposited On:18 Apr 2016 19:18
Last Modified:10 Nov 2021 23:55

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