Synthesis and properties of a novel molecular beacon containing a benzene-phosphate backbone at its stem moiety

Abstract

This paper describes the synthesis and properties of a novel molecular beacon (MB) containing a benzene-phosphate backbone at its stem moiety. The fluorescence intensity of MBs was found to stabilize by the introduction of the benzene-phosphate backbone at its stem moiety. Furthermore, an MB containing the benzene-phosphate backbone was more resistant to DNase I (endonuclease) than an MB comprising natural DNA and 2'-O-methyl-RNA. These results indicate that the MB with the benzene-phosphate backbone is superior as a molecular beacon as compared to the MB composed of natural DNA and 2'-O-methyl-RNA.

Synthesis and Properties of Oligonucleotides Containing Novel Fluorescent Biaryl Units

“…A solution of 3,5-bis(tert-butyldimethylsilyloxymethyl)phenylboronic acid (1.00 g, 2.44 mmol) [38] in THF/H 2 O (5:1, 12 mL) was added to a solution of 1-iodonaphthalene (0.62 g, 2.44 mmol) and PdCl 2 (dppf)·CH 2 Cl 2 (0.122 g, 0.149 mmol) in THF/H 2 O (5:1, 12 mL). NaOH (2 , 3.66 mL) was added to the mixture, and this mixture was stirred at 65°C for 24 h. The mixture was partitioned between EtOAc and H 2 O.…”

“…Arylboronic acid derivative 5, which was synthesized by a previously reported method, [38] was coupled with 1-iodonaphthalene (6) in the presence of PdCl 2 (dppf) [dppf = 1,1Ј-bis(diphenylphosphanyl)ferrocene] at 65°C; this coupling reaction afforded biaryl derivative 7; subsequently, 7 was desilylated upon treatment with tetra-n-butylammonium fluoride (TBAF) to give biaryl unit 3 in a yield of 84 %. One out of the two hydroxy groups of 3 was protected by a 4,4Ј-dimethoxytrityl (DMTr) group to give mono-DMTr derivative 8 in 37 % yield.…”

“…[37] Furthermore, we have designed and synthesized a molecular beacon (MB) that has the benzenephosphate backbone at the stem moiety; this MB successfully detected a target RNA with excellent efficiency. [38] The results of this study prompted us to examine the synthesis and properties of ONs that contain biaryl units composed of aromatic chromophores ( Figure 1). We speculated that since the structures of biaryl units 3 and 4 are such that interplanar angles are formed between the aromatic chromophores and the benzene moieties, the chromophores can efficiently stack on top of each other in DNA duplexes; as a result of this stacking, the duplexes will be thermally stabilized.…”

Nucleotides and nucleic acids; oligo- and polynucleotides

“…46 The phosphodiester backbone has also been replaced by a benzene-phosphate backbone for use in a molecular beacon. 47 PNA, first introduced in 1991 by Nielsen and co-workers, 48 is a neutral backbone modification wherein the normal DNA nucleobases are attached to an aminoethylglycine peptide backbone (10). PNA is commonly used as a peptide conjugate (see also oligonucleotide-peptide conjugates, section 3.1), the peptide portion used as a carrier for the PNA into cells.…”

“…207 Transcription of DNA containing 6-thioguanine under photolytic conditions combine to effectively irreversibly inhibit transcription by RNA pol II, possibly due to formation of guanine-6-sulfonate, which is a known inhibitor of transcription. 208 The S-functionalised thioguanine derivative (47) has been used to site-specifically modify the cytosine residue it is opposed to in duplex DNA. 209 The O6-position of guanine is readily alkylated and such lesions have also been the subject of much research over previous years, and a review of some of the major DNA lesions including O 6 -alkylguanine and 8-oxoguanine have been reported.…”