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A Monofunctional Platinum Complex Coordinated to a Rhodium Metalloinsertor Selectively Binds Mismatched DNA in the Minor Groove

Weidmann, Alyson G. and Barton, Jacqueline K. (2015) A Monofunctional Platinum Complex Coordinated to a Rhodium Metalloinsertor Selectively Binds Mismatched DNA in the Minor Groove. Inorganic Chemistry, 54 (19). pp. 9626-9636. ISSN 0020-1669. PMCID PMC4618505. doi:10.1021/acs.inorgchem.5b01722. https://resolver.caltech.edu/CaltechAUTHORS:20150928-090441652

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Abstract

We report the synthesis and characterization of a bimetallic complex derived from a new family of potent and selective metalloinsertors containing an unusual Rh–O axial coordination. This complex incorporates a monofunctional platinum center containing only one labile site for coordination to DNA, rather than two, and coordinates DNA nonclassically through adduct formation in the minor groove. This conjugate displays bifunctional, interdependent binding of mismatched DNA via metalloinsertion at a mismatch as well as covalent platinum binding. DNA sequencing experiments revealed that the preferred site of platinum coordination is not the traditional N7-guanine site in the major groove, but rather N3-adenine in the minor groove. The complex also displays enhanced cytotoxicity in mismatch repair-deficient and mismatch repair-proficient human colorectal carcinoma cell lines compared to the chemotherapeutic cisplatin, and it triggers cell death via an apoptotic pathway, rather than the necrotic pathway induced by rhodium metalloinsertors.


Item Type:Article
Related URLs:
URLURL TypeDescription
http://dx.doi.org/10.1021/acs.inorgchem.5b01722DOIArticle
http://pubs.acs.org/doi/suppl/10.1021/acs.inorgchem.5b01722PublisherSupporting Information
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4618505PubMed CentralArticle
ORCID:
AuthorORCID
Barton, Jacqueline K.0000-0001-9883-1600
Additional Information:© 2015 American Chemical Society. Received: July 29, 2015. Publication Date (Web): September 23, 2015. Financial support for this work from the NIH (GM33309) is gratefully acknowledged. We also thank the NIH for a training grant (NIH/NRSA 5T32GM7616-33) to A.G.W. The authors declare no competing financial interest.
Funders:
Funding AgencyGrant Number
NIHGM33309
NIH Predoctoral Fellowship5T32GM7616-33
Issue or Number:19
PubMed Central ID:PMC4618505
DOI:10.1021/acs.inorgchem.5b01722
Record Number:CaltechAUTHORS:20150928-090441652
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20150928-090441652
Official Citation:A Monofunctional Platinum Complex Coordinated to a Rhodium Metalloinsertor Selectively Binds Mismatched DNA in the Minor Groove Alyson G. Weidmann and Jacqueline K. Barton Inorganic Chemistry 2015 54 (19), 9626-9636 DOI: 10.1021/acs.inorgchem.5b01722
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:60563
Collection:CaltechAUTHORS
Deposited By: Tony Diaz
Deposited On:29 Sep 2015 03:14
Last Modified:10 Nov 2021 22:35

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