Synlett 2006(13): 2051-2054  
DOI: 10.1055/s-2006-948209
LETTER
© Georg Thieme Verlag Stuttgart · New York

Indole as an Artificial DNA Base Incorporated via an Acyclic 2′-Deoxyriboside Substitute

Claudia Wanninger, Hans-Achim Wagenknecht*
University of Regensburg, Institute for Organic Chemistry, Universitätsstr. 31, 93053 Regensburg, Germany
Fax: +49(941)9434617; e-Mail: achim.wagenknecht@chemie.uni-regensburg.de;
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Publikationsverlauf

Received 16 May 2006
Publikationsdatum:
09. August 2006 (online)

Abstract

Indole was synthetically incorporated into DNA as an artificial base at specific sites of duplex DNA. An acyclic substitute for the 2′-deoxyribose was applied in order to obtain a chemically stable nucleoside analogue that can be synthesized by a fast and facile procedure. Studies by methods of optical spectroscopy revealed that the indole base surrogate is intercalated into the DNA base stack and behaves as a universal base analogue with only little influence of the counterbase.

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Wagner, C.; Wagenknecht, H.-A. manuscript submitted for publication.

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Compound 3 was purified by flash chromatography with CH2Cl2:MeOH:Et3N = 100:3:0.1. Spectroscopic data of 3: 1H NMR (300 MHz, DMSO-d 6): δ = 2.99 (m, 6 H, OCH 2, CHOH, CH 2NH), 3.34 (m, 2 H, CH2-indole, masked under residual water in the sample), 3.73 (m, 8 H, OCH 3, NHCH 2CH2-indole), 6.87 (d, 4 H, arom. linker), 6.99 (m, 1 H, arom. indole), 7.08 (m, 1 H, arom. indole), 7.24 (m, 7 H, arom. linker), 7.39 (m, 2 H, arom. linker, 1 H arom. indole), 7.53 (m, 1 H, arom. indole), 10.95 (br s, 1 H, NH-indole).
13C NMR (75,4 MHz, DMSO-d 6): δ = 45.03 (CH2NH), 55.25 (OCH3), 66.06 (CH2O), 73.47 (CHOH), 111.68, 113.37, 118.43, 118.56, 121.29, 123.20, 124.13, 127.12, 127.92, 128.03, 129.95, 135.78, 135.83, 136.36, 145.13, 149.82, 158.26. HRMS (ESI): m/z calcd: 537.2753 [MH+]; found: 537.2761 [MH+].

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Interestingly, the trifluoroacetylated derivative of 3 shows two sets of NMR signals (due to cis/trans isomers of the immonium structure): 1H NMR (300 MHz, DMSO-d 6): δ = 2.90 (m, 3 H, OCH 2, CHOH), 3.35 (m, 2 H, NCH 2 linker), 3.64 (m, 2 H, NCH 2CH2-indole), 3.71 (m, 6 H, OCH 3), 4.01 (m, 2 H, NCH2CH 2-indole), 6.85 (m, 4 H, arom. linker), 6.93-7.17 (m, 2 H, arom. indole), 7.22 (m, 7 H, arom. linker), 7.45 (m, 3 H, arom.), 7.55 (d, 1 H, arom. indol), 10.86 (br s, 0.5 H, NH-indole, cis-isomer), 10.91 (br s, 0.5 H, NH-indole, trans-isomer).

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Indole extinction coefficient: ε260 = 4000 M-1cm-1 in MeOH.

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ESI ms data (negative mode): ssDNA1: m/z calcd: 5157.9 [M - H+]-; found: 1719.6 [M - 3 H+]3-; ssDNA2: m/z calcd: 5139.9 [M - H+]-; found: 1713.6 [M - 3 H+]3-; ssDNA3: m/z calcd: 5189.9 [M - H+]-; found: 1730,3 [M - 3 H+]3-; ssDNA4: m/z calcd: 5009.9 [M - H+]-; found: 1703.7 [M - 3 H+]3-.