Binding of phosphorothioate oligonucleotides to zwitterionic liposomes

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Although double-stranded DNA (dsDNA) has been shown to bind to zwitterionic lipids, it has been reported that this association is stronger for disordered (Lα) phase lipids than for well-ordered (Lβ) lipids. In this work, the interaction of single-strand phosphorothioate oligonucleotides (ONs) with unilamellar liposomes of saturated and unsaturated zwitterionic phosphocholines (PCs) and phosphoroethylamine (PE) was investigated. It is shown that the association of phosphorothioate ONs to diacyl glycerophosphocholines is strong, but only for Lβ phase or otherwise ordered bilayers. There is no measurable affinity for PE lipids. The apparent affinity of three different phosphorothioate ONs for Lβ phase 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) has been measured and the dissociation constants were on the order of 10-7 M. Purine-rich ON sequences had stronger binding to DPPC liposomes than did pyrimidine-rich sequences, but there were other sequence-dependent factors. This exceptionally high affinity could be an important consideration in ON uptake, delivery, and biodistribution. © 2002 Elsevier Science B.V. All rights reserved.




Lu, D., & Rhodes, D. G. (2002). Binding of phosphorothioate oligonucleotides to zwitterionic liposomes. Biochimica et Biophysica Acta - Biomembranes, 1563(1–2), 45–52.

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