Structure-activity relationships and cellular mechanism of action of small molecules that enhance the delivery of oligonucleotides.

ABSTRACT: The pharmacological effects of antisense and siRNA oligonucleotides are hindered by the tendency of these molecules to become entrapped in endomembrane compartments thus failing to reach their targets in the cytosol or nucleus. We have previously used high throughput screening to identify small molecules that enhance the escape of oligonucleotides from intracellular membrane compartments and have termed such molecules OECs (oligonucleotide enhancing compounds). Here, we report on the structure-activity relationships of a family of OECs that are analogs of a hit that emerged from our original screen. These studies demonstrate key roles for the lipophilic aromatic groups, the tertiary nitrogen, and the carbamate moiety of the parent compound. We have also investigated the intracellular site

SUBMITTER: Juliano RL 

PROVIDER: S-EPMC5829638 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature