Abstract
Cationic lipo-oligomers containing unsaturated oleic acid are potent siRNA carriers based on electrostatic and hydrophobic lipo-polyplex formation and endosomal membrane destabilization. Lipo-oligomers can be produced by solid-phase-supported synthesis in sequence-defined form. However, the trifluoroacetic acid (TFA)-mediated removal of acid-labile protecting groups and cleavage from the resin can be accompanied by side products caused by the addition of TFA to the double bonds of oleic acid. Under aqueous conditions, these TFA adducts of oleic acid are converted into hydroxystearic acid derivatives. The cleavage protocol was optimized to decrease TFA adducts. The pure oleic acid (C18:1) containing lipo-oligomer was compared with analogous structures containing saturated or modified hydrophobic moieties (stearic acid (C18:0), hydroxystearic acid, and 8-nonanamidooctanoic acid). The structure containing intact oleic acid shows favorable pH dependency of lytic activity, efficient gene silencing, and excellent cell tolerability relative to its counterparts.
Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
