Stabilization of Parallel Triplexes by Twisted Intercalating Nucleic Acids (TINAs) Incorporating 1,2,3-Triazole Units and Prepared by Microwave-Accelerated Click Chemistry
✍ Scribed by Imrich Géci; Vyacheslav V. Filichev; Erik B. Pedersen
- Publisher
- John Wiley and Sons
- Year
- 2007
- Tongue
- English
- Weight
- 401 KB
- Volume
- 13
- Category
- Article
- ISSN
- 0947-6539
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✦ Synopsis
Abstract
A highly efficient method for postsynthetic modification of unprotected oligonucleotides incorporating internal insertions of (R)‐1‐O‐(4‐ethynylbenzyl)glycerol has been developed through the application of click chemistry with water‐insoluble pyren‐1‐yl azide and water‐soluble benzyl azide and acceleration by microwave irradiation. The twisted intercalating nucleic acids (TINAs) obtained in these reactions, possessing bulged insertions of (R)‐3‐O‐{4‐[1‐(pyren‐1‐yl)‐1__H__‐1,2,3‐triazol‐4‐yl]benzyl}glycerol (7), formed parallel triplexes with thermal stabilities of 20.0, 34.0, and 40.0 °C at pH 7.2 in the cases of one, two, or three insertions of 7, respectively, separated by three nucleic bases. An oligonucleotide with four insertions of 7—each between three nucleic bases in the sequence—was unable to form complexes with complementary single‐ or double‐stranded DNAs, as a result of self‐aggregation of the pyrene moieties. This assumption was supported by the formation of a very strong excimer band at 460 nm in the fluorescence spectra. Molecular modeling of the parallel triplex with bulged insertion of the monomer 7 in the triplex‐forming oligonucleotide (TFO) showed that only the pyrene moiety was stacking between the bases of the dsDNA, whereas 1,2,3‐triazole did not participate in the triplex stabilization. Thermal denaturation studies of the duplexes and triplexes, as well as the fluorescence properties of TINA‐triazole 7, are discussed and compared with previous studies on TINA.