Precise Targeted Cleavage of a r(CUG) Repeat Expansion in Cells by Using a Small-Molecule-Deglycobleomycin Conjugate.

ABSTRACT: RNA repeat expansions cause more than 30 neurological and neuromuscular diseases with no known cures. Since repeat expansions operate via diverse pathomechanisms, one potential therapeutic strategy is to rid them from disease-affected cells, using bifunctional small molecules that cleave the aberrant RNA. Such an approach has been previously implemented for the RNA repeat that causes myotonic dystrophy type 1 [DM1, r(CUG)^exp] with Cugamycin, which is a small molecule that selectively binds r(CUG)^exp conjugated to a bleomycin A5 cleaving module. Herein, we demonstrate that, by replacing bleomycin A5 with deglycobleomycin, an analogue in which the carbohydrate domain of bleomycin A5 is removed, the selectivity of the resulting small-molecule conjugate (DeglycoCugamycin)

SUBMITTER: Angelbello AJ 

PROVIDER: S-EPMC7360342 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature