Dimeric diarylmercury-aptamer conjugates for LA-ICP-MS imaging
3.59 MB
avoin
Julkaisu on tekijänoikeussäännösten alainen. Teosta voi lukea ja tulostaa henkilökohtaista käyttöä varten. Käyttö kaupallisiin tarkoituksiin on kielletty.
Pysyvä osoite
Verkkojulkaisu
DOI
Tiivistelmä
Aptamers are synthetic single-chain DNA or RNA oligonucleotides capable of adopting stable 3D conformations and thus binding chosen targets tightly and with great specificity. Owing to the chemical tunability of their nucleic acid backbone, they can be functionalized at selected sites with small compounds, metal ions, or nanomaterial constructs for deployment in molecular imaging, diagnostics and targeted delivery applications. Aptamer based metal tagging is an emerging strategy to translate molecular recognition into spatially resolved elemental signals for mass spectrometric bioimaging. Laser ablation-inductively coupled plasma-mass spectrometry (LA-ICP-MS) is an elemental imaging technique that in a biological context enables quantitative, micrometer scale mapping of endogenous trace elements and exogenously introduced metal tagged biomarker species in two dimensions.
The goal of this study was to synthesize a stable diarylmercurial compound which would be suitable for aptamer conjugation followed by bioimaging. Initially a diarylmercury solid support with DMTr protecting group was synthesized, but it did not survive oxidative and acidic conditions.
Another, azide-linked, dimeric diarylmercury molecule was synthesized to avoid the above mentioned conditions. When separated from the analogous monoarylmercury molecule at room temperature, this compound demonstrated chemical stability. Single-stranded and double-helical oligonucleotides were utilized for conjugation, along with a recently created 76-mer DNA aptamer that is specific to GFAP. The aptamer attaches to the particular protein while bearing the metal tag when the dimeric diarylmercury-aptamer combination is administered to tissue that contains that particular protein. The presence of the protein can then be verified by using LA-ICP-MS to identify and visualize the metal tag.