A Photoreactive Ruthenium(II) Complex Tethered to a Guanine‐Containing Oligonucleotide: A Biomolecular Tool that Behaves as a “Seppuku Molecule”

Abstract

Selbstzerstörung: Durch das Anhängen eines photoreaktiven Ruthenium(II)‐Komplexes an ein guaninhaltiges Oligonucleotid entsteht ein neuartiges Hilfsmittel für Studien zur Genstummschaltung. Das Konjugat wird mit dem komplementären Strang selektiv photochemisch verknüpft, führt aber in Gegenwart eines nichtkomplementären Strangs eine Selbstinhibition aus („Seppuku“; siehe Bild). Auf diese Weise lassen sich unerwünschte sekundäre Photoeffekte vermeiden.

Light‐Triggered Green Fluorescent Protein Silencing in Human Keratinocytes in Culture Using Antisense Oligonucleotides Coupled to a Photoreactive Ruthenium(II) Complex

“…Moreover the Ru–ASO conjugates that contain a G base in their own sequence (Ru–ASO G ) exhibit a unique property 27. 28 Indeed, owing to the presence of a G unit in the probe sequence, an intramolecular photoreaction takes place in the absence of the complementary strand, and produces a cyclic photoadduct (Scheme b).…”

“…28 Indeed, owing to the presence of a G unit in the probe sequence, an intramolecular photoreaction takes place in the absence of the complementary strand, and produces a cyclic photoadduct (Scheme b). The occurrence of such a cyclic adduct is of great interest since it prevents side reactions towards a nontargeted sequence 27. A first in cellulo study has highlighted the potential of such Ru–ASO conjugates for “gene‐silencing” applications.…”

Photocrosslinking between Peptide–Peptide or Peptide–Oligonucleotide by RuII–TAP Complexes

“…[14] Our research group has examined the possibility of using Ru II complexes as DNA photoreagents for application in gene silencing. [15] In that case the Ru II compounds comprised two or three TAP (1,4,5,8-tetra-azaphenanthrene) ligands (Figure 1 A). Oligodeoxyribonucleotides (ODNs) derivatized with such photoreactive TAP complexes (Ru-ODN) [15] were designed to be complementary to the target sequence.…”

“…[15] In that case the Ru II compounds comprised two or three TAP (1,4,5,8-tetra-azaphenanthrene) ligands (Figure 1 A). Oligodeoxyribonucleotides (ODNs) derivatized with such photoreactive TAP complexes (Ru-ODN) [15] were designed to be complementary to the target sequence. After hybridization and illumination, the Ru-ODN was linked irreversibly to the target sequence, providAbstract: Ru II -TAP complexes have been shown to be very attractive compounds in the frame of developments of new anticancer drugs targeting the genetic material.…”

“…[15] These resulting photocrosslinkings could be used in gene silencing the targeted sequence. In fact, the special photoreactivity of the TAP complexes is responsible for this interesting behavior.…”