Development of bright fluorescent quadracyclic adenine analogues: TDDFT-calculation supported rational design
| Autor: | Christopher P. Lawson, Søren Preus, Marcus Wilhelmsson, Blaise Dumat, Henrik Gradén, Mattias Bood, Anders Foller Larsen, Morten Grøtli, Moa Sandberg Wranne |
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| Rok vydání: | 2015 |
| Předmět: |
Fluorophore
Base analog OLIGONUCLEOTIDES Article Fluorescence Fluorescence spectroscopy PROBES chemistry.chemical_compound NUCLEIC-ACID PYRROLO-DC Cytosine analog Fluorescent Dyes NUCLEOSIDE Multidisciplinary Adenine Rational design Time-dependent density functional theory Combinatorial chemistry CYTOSINE ANALOG Förster resonance energy transfer Biochemistry chemistry PHOTOPHYSICAL PROPERTIES DENSITY BASE ANALOG FLUOROPHORE |
| Zdroj: | Scientific Reports Larsen, A F, Dumat, B, Wranne, M S, Lawson, C P, Preus, S, Bood, M, Graden, H, Wilhelmsson, L M & Grøtli, M 2015, ' Development of bright fluorescent quadracyclic adenine analogues : TDDFT-calculation supported rational design ', Scientific Reports, vol. 5, 12653 . https://doi.org/10.1038/srep12653 |
| ISSN: | 2045-2322 |
| DOI: | 10.1038/srep12653 |
| Popis: | 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 (εΦF = 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. |
| Databáze: | OpenAIRE |
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