Pentacyclic adenine: a versatile and exceptionally bright fluorescent DNA base analog

Bood, M. et al. (2018) Pentacyclic adenine: a versatile and exceptionally bright fluorescent DNA base analog. Chemical Science, 9(14), pp. 3494-3502. (doi: 10.1039/C7SC05448C) (PMID:29780479) (PMCID:PMC5934695)

Abstract

Emissive base analogs are powerful tools for probing nucleic acids at the molecular level. Herein we describe the development and thorough characterization of pentacyclic adenine (pA), a versatile base analog with exceptional fluorescence properties. When incorporated into DNA, pA pairs selectively with thymine without perturbing the B-form structure and is among the brightest nucleobase analogs reported so far. Together with the recently established base analog acceptor qAnitro, pA allows accurate distance and orientation determination via Förster resonance energy transfer (FRET) measurements. The high brightness of its emission at wavelengths above 400 nm also makes it suitable for fluorescence microscopy, as demonstrated by imaging of single liposomal constructs coated with cholesterol-anchored pA-dsDNA, using total internal reflection fluorescence microscopy. Finally, pA is also highly promising for two-photon excitation at 780 nm, with a brightness (5.3 GM) that is unprecedented for a base analog.

• Item Type: Articles
• Additional Information: This work was supported by the Swedish Foundation for Strategic Research (SSF, grants No. ID14-0036, IS14-0041 and IRC15-0065) and the Swedish Research Council (VR, grant No. 2013-4375). BHK thanks the support of NRF of South Korea (2014R1A2A1A12067404). AHE-S was supported by UK BBSRC grant BB/J001694/2. RSF gratefully acknowledges PhD studentship funding from the Engineering and Physical Sciences Research Council (UK).
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Magennis, Dr Steven and Fisher, Rachel
• Authors: Bood, M., Füchtbauer, A. F., Wranne, M. S., Ro, J. J., Sarangamath, S., El-Sagheer, A. H., Rupert, D., Fisher, R. S., Magennis, S. W., Höök, F., Jones, A. C., Brown, T., Kim, B. H., Dahlen, A., Wilhelmsson, M., and Grotli, M.
• College/School: College of Science and Engineering > School of Chemistry
• Journal Name: Chemical Science
• Publisher: Royal Society of Chemistry
• ISSN: 2041-6520
• ISSN (Online): 2041-6539
• Published Online: 01 March 2018
• Copyright Holders: Copyright © 2018 The Royal Society of Chemistry
• First Published: First published in Chemical Science 9(14): 3494-3502
• Publisher Policy: Reproduced under a Creative Commons License