Automated Solid-Phase Synthesis of Site-Specifically Labeled Ruthenium−Oligonucleotides

Abstract

A novel metallonucleoside phosphoramidite is reported for the automated solid-phase synthesis of site-specifically metallolabeled oligonucleotides.

Fluorescent Analogs of Biomolecular Building Blocks: Design, Properties, and Applications

“…536–538 Enzymatic incorporation of these metal-containing triphosphates ( 6.101.g, 6.107.g, 6.114.g and 6.119.g ), by vent(exo-) and Pwo polymerases, produced modified oligonucleotides that were employed for SNP detection using luminescence (in case of Ru II containing oligonucleotides) or electrochemical detection (for Os II containing oligonucleotides) (Section 6.7) 536–538. Ru complexes have also been connected through a propargylamide linker to the 5-position of dU, yielding nucleosides with photophysical properties similar to the ones listed above 539,540. Tuning the redox potential of Ru and Os-containing nucleotides has been discussed 541…”

Metallocene–DNA: Synthesis, Molecular and Electronic Structure and DNA Incorporation of C5-Ferrocenylthymidine Derivatives

“…An alternative strategy is the synthesis of metal‐modified nucleosides as phosphoramidite monomers for use in automated solid‐phase synthesis 34. This approach has been well developed in organic chemistry but has only rather recently been explored for metal‐containing groups 7, 35–40. The advantages of this approach include the ease of synthesis and the ability to incorporate the modified base into the oligonucleotide sequence site‐specifically.…”

Solid-Phase Synthesis and Photophysical Properties of DNA Labeled at the Nucleobase with Ru(bpy)2(4-m-4‘-pa-bpy)2+

“…We synthesized a 5-[Ru(bpy) 2 (4-m-4′-pa-bpy)] 2+ -2′-deoxyuridine phosphoramidite and incorporated this derivatized uridine in an oligonucleotide using a standard reaction coupling protocol on an automated DNA synthesizer. 37 We selected this particular 5-[Ru(bpy) 2 (4-m-4′-pa-bpy)] 2+ -2′-deoxyuridine nucleoside since the excited state was known to be long-lived and localized on the bipyridine attached to the uridine. 39 This phosphoramidite approach is suited for synthesizing metallo-labeled oligonucleotides; however, it often requires the synthesis of large molecular weight nucleoside derivatives containing complex functional groups that are time-consuming to prepare and difficult to purify and handle.…”