Development of bright fluorescent quadracyclic adenine analogues: TDDFT-calculation supported rational design
Artikel i vetenskaplig tidskrift, 2015

Fluorescent base analogues (FBAs) comprise a family of increasingly important molecules for the investigation of nucleic acid structure and dynamics. We recently reported the quantum chemical calculation supported development of four microenvironment sensitive analogues of the quadracyclic adenine (qA) scaffold, the qANs, with highly promising absorptive and fluorescence properties that were very well predicted by TDDFT calculations. Herein, we report on the efficient synthesis, experimental and theoretical characterization of nine novel quadracyclic adenine derivatives. The brightest derivative, 2-CNqA, displays a 13-fold increased brightness (epsilon Phi(F) = 4500) compared with the parent compound qA and has the additional benefit of being a virtually microenvironment-insensitive fluorophore, making it a suitable candidate for nucleic acid incorporation and use in quantitative FRET and anisotropy experiments. TDDFT calculations, conducted on the nine novel qAs a posteriori, successfully describe the relative fluorescence quantum yield and brightness of all qA derivatives. This observation suggests that the TDDFT-based rational design strategy may be employed for the development of bright fluorophores built up from a common scaffold to reduce the otherwise costly and time-consuming screening process usually required to obtain useful and bright FBAs.

Fluorophore

Base Analog

Probes

Photophysical Properties

Pyrrolo-Dc

Density

Cytosine Analog

Nucleic-Acid

Nucleoside

Oligonucleotides

Författare

Anders Foller Füchtbauer

Chalmers, Kemi och kemiteknik, Kemi och biokemi, Fysikalisk kemi

Blaise Dumat

Chalmers, Kemi och kemiteknik, Kemi och biokemi, Fysikalisk kemi

Moa Sandberg Wranne

Chalmers, Kemi och kemiteknik, Kemi och biokemi, Fysikalisk kemi

Christopher Lawson

Göteborgs universitet

S. Preus

Aarhus Universitet

Mattias Bood

Göteborgs universitet

Henrik Gradén

AstraZeneca AB

Marcus Wilhelmsson

Chalmers, Kemi och kemiteknik, Kemi och biokemi, Fysikalisk kemi

Morten Grötli

Göteborgs universitet

Scientific Reports

2045-2322 (ISSN)

Vol. 5 art. no. 12653- 12653

Styrkeområden

Nanovetenskap och nanoteknik

Livsvetenskaper och teknik

Ämneskategorier

Fysikalisk kemi

Biokemi och molekylärbiologi

Organisk kemi

DOI

10.1038/srep12653