Accueil > Publications > Recherche par années > Années 2000 > 2005

Brunet, E ; Corgnali, M ; Perrouault, L ; Roig, V ; Asseline, U ; Sorensen, MD ; Babu, BR ; Wengel, J ; Giovannangeli, C

Intercalator conjugates of pyrimidine locked nucleic acid-modified triplex-forming oligonucleotides : improving DNA binding properties and reaching cellular activities

Nucleic Acids Research 33 (13) 4223-4234

par Administrateur - publié le

Abstract :

Triplex-forming oligonucleotides (TFOs) are powerful tools to interfere sequence-specifically with DNA-associated biological functions. (A/T,G)-containing TFOs are more commonly used in cells than (T,C)-containing TFOs, especially C-rich sequences ; indeed the low intracellular stability of the non-covalent pyrimidine triplexes make the latter less active. In this work we studied the possibility to enhance DNA binding of (T,C)-containing TFOs, aiming to reach cellular activities ; to this end, we used locked nucleic acid-modified TFOs (TFO/LNAs) in association with 5’-conjugation of an intercalating agent, an acridine derivative. In vitro a stable triplex was formed with the TFO-acridine conjugate : by SPIR measurements at 37 degrees C and neutral pH, the dissociation equilibrium constant was found in the nanomolar range and the triplex half-life similar to 10 h (50-fold longer compared with the unconjugated TFO/ LNA).