Séminaire du Département de Biologie Structurale & Chimie
Jeudi 7 Septembre 2017 à 14h00
Salle JULES BORDET – Metchnikoff RdC 45
Pr Christian LEUMANN
University of Bern
A revival of bicyclo-DNA
In the early nineties we introduced the concept of conformational restriction with the example of bicyclo-DNA (bc-DNA), resulting in oligonucleotide structures the show reduced entropic penalty upon duplex formation. This concept has been adapted by others and has produced excellent oligonucleotide drug candidates such as locked-nucleic acids (LNA) and hexitol nucleic acids (HNA).These analogues typically exhibit increased affinity to RNA and feature higher nuclease resistance.
While in this way the challenges linked to target affinity and nuclease resistance have largely been met, other requirements such as improving cellular uptake and distribution are yet elusive. In the context of oligonucleotide therapeutics our laboratory has developed over the years the bicyclo-DNA molecular platform. The 5-membered carbocyclic ring in bicyclo-DNA offers unique possibilities for further chemical modification, specifically at C(6’) and C(7’), to introduce additional functional groups for various purposes. In recent work we reported on the DNA and RNA affinity of oligonucleotides containing 7ˈ,5ˈ-bicyclo-nucleoside units. We have also investigated the properties of the corresponding 7ˈ,5ˈ-bicyclo-nucleoside triphosphate as a potential XNA candidate to generate modified aptamers.
Contact: Marcel HOLLENSTEIN / DBSC