Synthesis of an Unlocked Nucleic Acid Terpyridine Monomer and Binding of Divalent Metal Ion in Nucleic Acid Duplexes

Abstract

Herein we present the synthesis and thermal stability studies of modified oligonucleotides containing an unlocked nucleic acid (UNA) terpyridine monomer. Incorporation of this monomer into both strands of a DNA duplex allowed reversible thermal stability modulation upon addition or withdrawal of divalent metal ions. A likely explanation of this phenomenon is interstrand complexation between two terpyridine units and a metal ion. This system could be useful in the development of nanoscale devices based on DNA hybridization.

Pyrene‐Modified Unlocked Nucleic Acids: Synthesis, Thermodynamic Studies, and Fluorescent Properties

“…(2): Pyrene-1-carboxylic acid (111 mg, 0.451 mmol) was dissolved in anhydrous DMF (2 mL), and DIPEA (0.8 mL, 4.6 mmol) and HATU (235 mg, 0.617 mmol) were added. The resulting mixture was stirred for 35 min at RT and subsequently added dropwise to a solution of nucleoside 1 [15] (280.0 mg, 0.383 mmol) in anhydrous DMF (1.5 mL). The mixture was stirred for 1.5 h at RT and was then diluted with EtOAc (100 mL), washed with sat.…”

“…Compound 2 was synthesized by treatment of compound 1 [15] with pyrene-1-carboxylic acid and 2-(7-aza-1H-benzotriazol-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate (HATU) in DMF. Desilylation of compound 2 by treatment with TBAF in THF afforded derivative 4, which upon O3'-phosphitylation with diisopropylammonium tetrazolide (DIHT) and 2-cyanoethyl N,N,N',N'-tetraisopropylphosphorodiamidite in anhydrous dichloromethane (DCM) was converted into phosphoramidite 6.…”

“…Desilylation of compound 2 by treatment with TBAF in THF afforded derivative 4, which upon O3'-phosphitylation with diisopropylammonium tetrazolide (DIHT) and 2-cyanoethyl N,N,N',N'-tetraisopropylphosphorodiamidite in anhydrous dichloromethane (DCM) was converted into phosphoramidite 6. Compound 3 was obtained by reductive amination of UNA derivative 1 [15] by treatment with pyrene-1-carbaldehyde and sodium triacetoxyborohydride in DCE. Subsequent desilylation to give compound 5, followed by O3'-phosphitylation with DIHT and 2-cyanoethyl N,N,N',N'-tetraisopropylphosphorodiamidite in anhydrous DCM, afforded phosphoramidite 7.…”

“…Recently, we have introduced a piperazino derivative of UNA with the piperazine ring attached to the C2' atom of a UNA-U monomer. [15] The piperazino group primarily acts as a convenient handle for conjugaTwo pyrene-modified UNA monomers were synthesized and incorporated into 21-mer DNA oligonucleotides. Melting temperatures and thermodynamic properties of the modified duplexes were measured, and the fluorescence properties of single strands and duplexes containing one or more pyrene-UNA modifications were studied.…”

Non-nucleosidic analogs of nucleic acids

“…The derivatives with a piperazine group (Karlsen et al, 2009;Karlsen et al, 2012) are among the possible linkers of useful ligands, including a terpyridine ligand for metal chelation (Karlsen et al, 2009;Karlsen et al, 2012).…”