Luminescent pyrenyl-GNA nucleosides: synthesis, photophysics and confocal microscopy studies in cancer HeLa cells.

Abstract

Glycol nucleic acids (GNA) are synthetic genetic-like polymers with an acyclic three-carbon propylene glycol phosphodiester backbone. Here, synthesis, luminescence properties, circular dichroism (CD) spectra, and confocal microscopy speciation studies of (R,S) and (S,R) pyrenyl-GNA (pyr-GNA) nucleosides are reported in HeLa cells. Enantiomerically pure nucleosides were obtained by a Sharpless asymmetric dihydroxylation reaction followed by semi-preparative high-performance liquid chromatography (HPLC) separation using Amylose-2 as the chiral stationary phase. The enantiomeric relationship between stereoisomers was confirmed by CD spectra, and the absolute configurations were assigned based on experimental and theoretical CD spectra comparisons. The pyr-GNA nucleosides were not cytotoxic against human cervical (HeLa) cancer cells and thus were utilized as luminescent probes in the imaging of these cells with confocal microscopy. Cellular staining patterns were identical for both enantiomers in HeLa cells. Compounds showed no photocytotoxic effect and were localized in the lipid membranes of the mitochondria, in cellular vesicles and in other lipid cellular compartments. The overall distribution of the pyrene and pyrenyl-GNA nucleosides inside the living HeLa cells differed, since the former compound gives a more granular staining pattern and the latter a more diffuse one.

• Authors: Joanna Skiba , Aleksandra Kowalczyk , Marta A Fik , Magdalena Gapińska , Damian Trzybiński , Krzysztof Woźniak , Valerije Vrček , Rafał Czerwieniec , Konrad Kowalski
• Journal: Photochemical & photobiological sciences : Official journal of the European Photochemistry Association and the European Society for Photobiology (Photochem Photobiol Sci) Vol. 18 Issue 10 Pg. 2449-2460 (Oct 09 2019) ISSN: 1474-9092 [Electronic] England
• PMID: 31407765 (Publication Type: Journal Article)

Chemical References

• Fluorescent Dyes
• Glycols
• Nucleic Acids
• Nucleosides
• Pyrenes
• pyrene

Topics

• Cell Survival (drug effects)
• Circular Dichroism
• Crystallography, X-Ray
• Density Functional Theory
• Fluorescent Dyes (chemical synthesis, chemistry)
• Glycols (chemistry)
• HeLa Cells
• Humans
• Microscopy, Confocal
• Molecular Conformation
• Nucleic Acids (chemistry)
• Nucleosides (chemical synthesis, chemistry, pharmacology)
• Pyrenes (chemistry)
• Stereoisomerism