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Sequence-Defined Cationic Lipo-Oligomers Containing Unsaturated Fatty Acids for Transfection

  • Sören ReinhardEmail author
  • Ernst Wagner
Protocol
Part of the Methods in Molecular Biology book series (MIMB, volume 1943)

Abstract

Sequence-defined cationic lipo-oligomers containing unsaturated fatty acids are potent nucleic acid carriers that are produced by solid-phase supported synthesis. 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 an addition of TFA to the double bonds of unsaturated fatty acids. These TFA adducts are converted into hydroxylated derivatives under aqueous conditions. Here we describe an optimized cleavage protocol (precooling cleavage solution to 4 °C, 20 min cleavage at 22 °C), which minimizes TFA adduct formation, retains the unsaturated hydrocarbon chain character, and ensures high yields of the synthesis.

Key words

Nucleic acid delivery Polyplexes Sequence-defined Solid phase synthesis Oleic acid 

Notes

Acknowledgments

This work was supported by DFG SFB1032 B4 (to E.W.), SFB1066 B5 (E.W.), DFG FOR1406 (E.W.) and DFG Excellence Cluster Nanosystems Initiative Munich (E.W.).

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Authors and Affiliations

  1. 1.Department of Pharmacy, Pharmaceutical BiotechnologyCenter of Nanoscience (CeNS), Ludwig-Maximilians-Universität ButenandtstrMünchenGermany
  2. 2.Nanosystems Initiative Munich (NIM)SchellingstrMünchenGermany

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