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Targeting DNA Mismatches with Coordination Complexes

Barton, Jacqueline K. and Boynton, Adam N. and Boyle, Kelsey M. (2018) Targeting DNA Mismatches with Coordination Complexes. In: DNA-targeting Molecules as Therapeutic Agents. Royal Society of Chemistry , Cambridge, pp. 367-390. ISBN 978-1-78262-992-4. http://resolver.caltech.edu/CaltechAUTHORS:20180309-071202119

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Abstract

DNA base pair mismatches occur naturally in cells as a result of incorporation errors and damage. Most cells are able to identify and correct these mistakes before replication, allowing for high genome fidelity between cellular generations. In some forms of cancer, however, proteins involved in the machinery of mismatch repair (MMR) undergo mutation, making those cells unable to correct mismatches and leading to an increase in mutations. Since higher mismatch frequency serves as an early indicator of cancer progression, for many researchers mismatches have provided a novel target for the design of organic and inorganic small-molecule therapeutics. In particular, transition metal complexes have shown great promise in this context owing to their valuable spectroscopic and photophysical properties and flexibility with respect to modification of their coordination spheres. Thus far, experimental designs have ranged from targeting the thermodynamic destabilization of mismatched sites to the hydrogen-bonding pattern of specific mismatched base pairs. Here, we review the diversity, practical application, and evolution of mismatch-targeting small molecules, with an emphasis on rhodium metalloinsertors and luminescent ruthenium compounds. Importantly, we highlight the discovery of metalloinsertion, a noncovalent DNA binding mode that is specific towards destabilized sites, such as mismatches, within the DNA duplex.


Item Type:Book Section
Related URLs:
URLURL TypeDescription
https://doi.org/10.1039/9781788012928-00367DOIArticle
http://pubs.rsc.org/en/Content/Chapter/9781788012928-00367/978-1-78801-292-8PublisherArticle
ORCID:
AuthorORCID
Barton, Jacqueline K.0000-0001-9883-1600
Boynton, Adam N.0000-0003-4427-513X
Boyle, Kelsey M.0000-0002-6728-8403
Additional Information:© 2018 The Royal Society of Chemistry. Print publication date: 12 Mar 2018. We are grateful to our many coworkers and collaborators for their efforts in carrying out the research described. We thank also the NIH, Moore Foundation, and Amgen for their financial support of this research.
Funders:
Funding AgencyGrant Number
NIHUNSPECIFIED
Gordon and Betty Moore FoundationUNSPECIFIED
AmgenUNSPECIFIED
Record Number:CaltechAUTHORS:20180309-071202119
Persistent URL:http://resolver.caltech.edu/CaltechAUTHORS:20180309-071202119
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:85215
Collection:CaltechAUTHORS
Deposited By: Tony Diaz
Deposited On:09 Mar 2018 15:56
Last Modified:26 Apr 2019 21:42

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