| 1. |
- Dumat, Blaise, 1984, et al.
(författare)
-
Second-Generation Fluorescent Quadracyclic Adenine Analogues: Environment-Responsive Probes with Enhanced Brightness
- 2015
-
Ingår i: Chemistry - A European Journal. - : Wiley. - 0947-6539 .- 1521-3765. ; 21:10, s. 4039-4048
-
Tidskriftsartikel (refereegranskat)abstract
- Fluorescent base analogues comprise a group of increasingly important molecules for the investigation of nucleic acid structure, dynamics, and interactions with other molecules. Herein, we report on the quantum chemical calculation aided design, synthesis, and characterization of four new putative quadracyclic adenine analogues. The compounds were efficiently synthesized from a common intermediate through a two-step pathway with the Suzuki-Miyaura coupling as the key step. Two of the compounds, qAN1 and qAN4, display brightnesses (εΦF) of 1700 and 2300, respectively, in water and behave as wavelength-ratiometric pH probes under acidic conditions. The other two, qAN2 and qAN3, display lower brightnesses but exhibit polarity-sensitive dual-band emissions that could prove useful to investigate DNA structural changes induced by DNA-protein or -drug interactions. The four qANs are very promising microenvironment-sensitive fluorescent adenine analogues that display considerable brightness for such compounds. Polarity and pH probes: 2-Aminopurine has long been the standard for fluorescent base analogues. Four new fluorescent probes suitable for the replacement of adenine in nucleic acids are presented. Based on their high structural similarity to their parent compound, quadracyclic adenine, they have the potential to be excellent A analogues. Their improved photophysical properties also suggest that they could be significantly brighter than 2-aminopurine inside nucleic acid systems (see figure; ΦF: fluorescence quantum yield).
|
|
| 2. |
- Larsen, Anders Foller, 1984, et al.
(författare)
-
Development of bright fluorescent quadracyclic adenine analogues: TDDFT-calculation supported rational design
- 2015
-
Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 5
-
Tidskriftsartikel (refereegranskat)abstract
- 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.
|
|
| 3. |
- Lawson, Christopher, 1968, et al.
(författare)
-
Synthesis, oligonucleotide incorporation and fluorescence properties in DNA of a bicyclic thymine analogue
- 2018
-
Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 8
-
Tidskriftsartikel (refereegranskat)abstract
- Fluorescent base analogues (FBAs) have emerged as a powerful class of molecular reporters of location and environment for nucleic acids. In our overall mission to develop bright and useful FBAs for all natural nucleobases, herein we describe the synthesis and thorough characterization of bicyclic thymidine (bT), both as a monomer and when incorporated into DNA. We have developed a robust synthetic route for the preparation of the bT DNA monomer and the corresponding protected phosphoramidite for solid-phase DNA synthesis. The bT deoxyribonucleoside has a brightness value of 790 M(-1)cm(-1) in water, which is comparable or higher than most fluorescent thymine analogues reported. When incorporated into DNA, bT pairs selectively with adenine without perturbing the B-form structure, keeping the melting thermodynamics of the B-form duplex DNA virtually unchanged. As for most fluorescent base analogues, the emission of bT is reduced inside DNA (4.5- and 13-fold in single- and double-stranded DNA, respectively). Overall, these properties make bT an interesting thymine analogue for studying DNA and an excellent starting point for the development of brighter bT derivatives.
|
|
| 4. |
- Lawson, Christopher, 1968, et al.
(författare)
-
Synthesis and photophysical characterisation of new fluorescent triazole adenine analogues
- 2014
-
Ingår i: Organic & Biomolecular Chemistry. - : Royal Society of Chemistry (RSC). - 1477-0520 .- 1477-0539. ; 12:28, s. 5158-5167
-
Tidskriftsartikel (refereegranskat)abstract
- Fluorescent nucleic acid base analogues are powerful probes of DNA structure. Here we describe the synthesis and photo-physical characterisation of a series of 2-(4-amino-5-(1H-1,2,3-triazol-4-yl)-7H-pyrrolo-[2,3-d] pyrimidin-7-yl) and 2-(4-amino-3-(1H-1,2,3-triazol-4-yl)-1H-pyrazolo[3,4-d] pyrimidin-1-yl) analogues via Sonogashira cross-coupling and [3 + 2]-cycloaddition reactions as the key steps in the synthesis. Compounds with a nitrogen atom in position 8 showed an approximately ten-fold increase in quantum yield and decreased Stokes shift compared to analogues with a carbon atom in position 8. Furthermore, the analogues containing nitrogen in the 8-position showed a more red-shifted and structured absorption as opposed to those which have a carbon incorporated in the same position. Compared to the previously characterised C8-triazole modified adenine, the emissive potential was significantly lower (tenfold or more) for this new family of triazoles-adenine compounds. However, three of the compounds have photophysical properties which will make them interesting to monitor inside DNA.
|
|
| 5. |
- Redwan, Itedale Namro, 1981, et al.
(författare)
-
Solid-Phase Synthesis of 5 '-O- N-(Acyl)sulfamoyl adenosine Derivatives
- 2012
-
Ingår i: European Journal of Organic Chemistry. - : Wiley. - 1434-193X .- 1099-0690. ; 2012:19, s. 3665-3669
-
Tidskriftsartikel (refereegranskat)abstract
- The solid-phase synthesis of 5'-O-[N-(acyl)sulfamoyl]adenosine derivatives is described. The use of a Rink amide polystyrene solid support together with an appropriately protected ribo-purine starting material allowed for the development of a highly reliable and practical route for the solid-phase synthesis of 5'-O-[N-(acyl)sulfamoyl]adenosines. The developed procedure enables the efficient parallel synthesis of the target compounds in high yields. These compounds are non-hydrolysable isosteres of acyl-adenylates, which play an important role in a range of different metabolic pathways such as ribosomal and non-ribosomal peptide synthesis, fatty acid oxidation or enzyme regulation; some adenylate-forming enzymes are potential drug targets.
|
|
| 6. |
- Redwan, Itedale Namro, 1981, et al.
(författare)
-
Synthesis and photophysical characterization of 1-and 4-(purinyl) triazoles
- 2013
-
Ingår i: Tetrahedron. - : Elsevier BV. - 0040-4020. ; 69:42, s. 8857-8864
-
Tidskriftsartikel (refereegranskat)abstract
- Fluorescent adenine mimetics are useful tools for studying DNA, RNA and enzyme functions. Herein we describe the synthesis of eight 1-(purinyl)triazoles and two 4-(purinyl)triazoles utilizing the 1,4-regioselective copper-catalyzed azide-alkyne cycloaddition (CuAAC) reaction as the key step. The fluorescence properties of five of the synthesized 1-(purinyl)triazoles are also presented. The five measured compounds displayed low quantum yields. The results, when compared to previously published data, suggest a high influence of the substitution pattern of the triazole on the fluorescence properties.
|
|
