Modulation of BACE1 Activity by Chemically Modified Aptamers

Cecile Gasse (1) , Marwa Zaarour (1) , Sam Noppen (2) , Mikhail Abramov (2) , Philippe Marliere , Sandra Liekens (2) , Bart de Strooper (3, 2, 4) , Piet Herdewijn (1, 2)

1 UMR 8030 - Génomique métabolique
2 KU Leuven - Catholic University of Leuven = Katholieke Universiteit Leuven
3 VIB Center for Brain & Disease Research [Leuven, Belgium]
4 UCL - University College of London [London]

A modified DNA aptamer that binds BACE1, a therapeutic target involved in Alzheimer's disease has been developed. This ssXNA not only tightly binds to BACE1 but also inhibits its protease activity in vitro in the same range as a previously described unmodified aptamer. We report the in vitro selection of functional oligonucleotides incorporating two nucleobase modifications 5-chlorouracil and 7-deazaadenine. The nucleoside analogue 5-chloro-2-deoxyuridine has already been explored as a replacement for thymidine in a chemically modified genome of a bacterium. Thus, 5-chlorouracil modification is a good candidate to support genetic transfer in vivo as well as functional activity.

Mots clés: aptamers; BACE1; inhibitors; secretases; XNA

Domaines: Sciences du Vivant [q-bio]

Cecile Gasse, Marwa Zaarour, Sam Noppen, Mikhail Abramov, Philippe Marliere, et al.. Modulation of BACE1 Activity by Chemically Modified Aptamers. ChemBioChem, 2018, 19 (7), pp.754-763. ⟨10.1002/cbic.201700461⟩. ⟨cea-02291360⟩