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. 2011 Sep 28;133(38):14912-5.
doi: 10.1021/ja206095a. Epub 2011 Sep 2.

Emissive RNA alphabet

Dongwon Shin  1 , Renatus W Sinkeldam, Yitzhak Tor
Affiliations

Emissive RNA alphabet

Dongwon Shin et al. J Am Chem Soc. .

Abstract

A fluorescent ribonucleoside alphabet consisting of highly emissive purine ((th)A, (th)G) and pyrimidine ((th)U, (th)C) analogues, all derived from thieno[3,4-d]pyrimidine as the heterocyclic nucleus, is described. Structural and biophysical analyses demonstrated that the emissive analogues are faithful isomorphic nucleoside surrogates. Photophysical analysis established that the nucleosides offer highly desirable qualities, including visible emission, high quantum yield, and responsiveness to environmental perturbations, traits entirely lacking in their native counterparts.

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Figures

Figure 1
Figure 1
Emissive RNA Alphabet.
Figure 2
Figure 2
X-ray crystal structures of thieno[3,4-d]pyrimidine analogs: a) thA, b) thC, c) thGdmf and d) thU.
Figure 3
Figure 3
Comparison of the X-ray crystal structure of thA with adenosine (ADENOS10 from CCDC): a) overlay of the ribose rings (rms 0.0521 Å), b) overlay of the nucleobases (rms 0.157 Å).
Figure 4
Figure 4
a) Absorption (dashed lines) and emission (solid lines) spectra of thA (green), thC (purple), thG (orange), and thU (blue) in water. b) Absorption (dashed lines) and emission (solid lines) spectra of thU in water (blue) and dioxane (red) and mixtures thereof (10, 30, and 70 v/v % water in dioxane, black lines). Emission intensities are corrected to reflect an optical density of 0.1 at λex. c) Stokes shift vs. ET(30) correlations for purines thA (solid squares) and thG (open squares), and d) Stokes shift vs. ET(30) correlations for pyrimidines thC (solid circles) and thU (open circles). The orange lines represent linear fits. Note: the data point for thA in dioxane [ET (30) = 36.0 kcal mol−1] has been excluded from linearization.,
Figure 5
Figure 5
Thermal melts of thG-containing RNA. All samples are containing 1.0 uM of each oligo, 20 mM Na cacodylate, 100 mM NaCl, 0.5 mM EDTA and pH 7.0. a) Absorbance vs. temperature denaturation profiles, b) Comparison of Tm values for duplexes of containing thG (1a) and G (1b) with their complementary and mismatched bases. Errors of two independent Tm measurements were less than 0.6 °C.
Scheme 1
Scheme 1
Syntheses of thG and thC.a a Reagents and conditions: (a) (i) chloroformamidine hydrochloride, DMSO2, 125 °C, 77 %; (ii) dimethylformamide dimethyl acetal, DMF, 98 %; (b) β-D-ribofuranose 1-acetate 2,4,5-tribenzoate, SnCl4, MeNO2, 65 °C, 64 %; (c) NH3/MeOH, 65 °C, 84 %; (d) (i) dimethylformamide dimethyl acetal, DMF, 77 %; (ii) DMTrCl, Py, 70 %; (iii) TOMCl, tBu2SnCl2, iPr2NEt, DCE, 13 %; (iv) 2-cyanoethyl N,N-diisopropylchloro phophoramidite, iPr2NEt, DCM, 0 °C–RT, 67%.; (e) 2,4,6-triisopropylbenzenesulfonyl chloride, TEA, DMAP, CH2Cl2; (f) NH3/MeOH, 70 °C, 37 % over 2 steps.–
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References

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    1. Kool has reported a complete set of emissive expanded RNA nucleoside analogs Hernández AR, Kool ET. Org. Lett. 2011;13:676–679.

    1. Fused heteroaromatics are known to be emissive. See: Wettack FS, Klapthor R, Shedd A, Koeppe M, Janda K, Dwyer P, Stratton K. The photophysics of several condensed ring heteroaromatic compounds. NBS Special Publication (United States) 1978;526:60–62. Zander M, Kirsch GZ. Naturforsch. 1989;44a:205–209.

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