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      A Rhodium-Cyanine Fluorescent Probe: Detection and Signaling of Mismatches in DNA

      1 , 1 , 1

      Journal of the American Chemical Society

      American Chemical Society (ACS)

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          Abstract

          <p class="first" id="P1">We report a bifunctional fluorescent probe that combines a rhodium metalloinsertor with a cyanine dye as the fluorescent reporter. The conjugate shows weak luminescence when free in solution or with well matched DNA but exhibits a significant luminescence increase in the presence of a 27-mer DNA duplex containing a central CC mismatch. DNA photocleavage experiments demonstrate that, upon photoactivation, the conjugate cleaves the DNA backbone specifically near the mismatch site on a 27-mer fragment, consistent with mismatch targeting. Fluorescence titrations with the 27-mer duplex containing the CC mismatch reveal a DNA binding affinity of 3.1 × 10 <sup>6</sup> M <sup>−1</sup>, similar to that of other rhodium metalloinsertors. Fluorescence titrations using genomic DNA extracted from various cell lines demonstrate a clear discrimination in fluorescence between those cell lines that are proficient or deficient in mismatch repair. This differential luminescence reflects the sensitive detection of the mismatch repair-deficient phenotype. </p><p id="P2"> <div class="figure-container so-text-align-c"> <img alt="" class="figure" src="/document_file/6e1c998a-3f91-4209-9156-313eedae896e/PubMedCentral/image/nihms942611u1.jpg"/> </div> </p>

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          Author and article information

          Journal
          Journal of the American Chemical Society
          J. Am. Chem. Soc.
          American Chemical Society (ACS)
          0002-7863
          1520-5126
          November 17 2017
          December 06 2017
          November 21 2017
          December 06 2017
          : 139
          : 48
          : 17301-17304
          Affiliations
          [1 ]Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, California 91125, United States
          Article
          10.1021/jacs.7b10639
          5892186
          29136382
          © 2017
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