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Rhodium-cyanine fluorescent probes for detection and signaling of mismatches in DNA

Nano, Adela and Barton, Jacqueline (2017) Rhodium-cyanine fluorescent probes for detection and signaling of mismatches in DNA. In: 254th American Chemical Society National Meeting & Exposition, August 20-24, 2017, Washington, DC.

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Mismatched (non-Watson-Crick) base pair damage in DNA occurs naturally from errors during the replication process. Deficiencies in the mismatch repair (MMR) machinery, a DNA repair pathway, strongly predispose cells to cancer development. Therefore, efficiently detecting DNA mismatches will greatly enable early detection of MMR-deficient precancerous cells. Herein, we report the synthesis and characterization of a bifunctional fluorescent probe that combines a rhodium metalloinsertor with indol trimethine cyanine, Cy(3), the luminescent reporter, via a PEG-type linker. The conjugate displays low luminescence when free in soln. or in the presence of well-matched DNA but exhibits a luminescence increase up to 9-fold in the presence of a 27-mer oligonucleotide contg. a central CC mismatch. DNA photocleavage expts. demonstrate that upon photoactivation, the conjugate can cleave the DNA backbone near the mismatch site on a 27-mer oligonucleotide, thus providing further evidence for mismatch targeting. Fluorescence titrns. of the Rh conjugate with genomic DNA (gDNA) extd. from MMR-deficient and MMR-proficient HCT116 cell lines show a luminescence differential between gDNA from MMR-deficient and - proficient cell lines, reflecting the sensitive detection of differences in mismatch frequency.

Item Type:Conference or Workshop Item (Paper)
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URLURL TypeDescription Website
Nano, Adela0000-0002-1984-5770
Barton, Jacqueline0000-0001-9883-1600
Additional Information:© 2017 American Chemical Society.
Record Number:CaltechAUTHORS:20170912-100733809
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Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:81350
Deposited By: Tony Diaz
Deposited On:12 Sep 2017 17:54
Last Modified:03 Oct 2019 18:41

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