Amino Acid–Nucleotide–Lipids: Effect of Amino Acid on the Self-Assembly Properties

Hybrid amphiphiles composed of a lipid covalently linked to biomolecules are attracting considerable attention, owing to their unique physicochemical and biological properties. Herein, we have synthesized novel amino acid–nucleotide–lipids (ANLs), presenting phenylalanine and thymidine residues and saturated or unsaturated diacyl glycerol lipid moieties to investigate the effect of the specific aminoacid moieties on both aggregation properties and interactions of ANLs with single strand polyA RNA. Physicochemical studies (DLS, cryo-TEM, and small angle X-ray scattering) indicate that phenylanaline amino acids inserted at the 5′ position of the nucleotide-lipids stabilize multilamellar systems, whereas unilamellar vesicles are formed preferentially in the case of nucleotide–lipids (NLs). Both NLs and ANLs exhibit weak interactions with complementary polyA RNA as revealed by isothermal titration calorimetry investigations. The multilamellar vesicles obtained with ANLs could be used as a versatile carrier, suitable for both hydrophobic and hydrophilic therapeutic molecules

Unexpected Bilayer Formation in Langmuir Films of Nucleolipids

Langmuir monolayers have been extensively investigated by various experimental techniques. These studies allowed an in-depth understanding of the molecular conformation in the layer, phase transitions, and the structure of the multilayer. As the monolayer is compressed and the surface pressure is increased beyond a critical value, usually occurring in the minimal closely packed molecular area, the monolayer fractures and/or folds, forming multilayers in a process referred to as collapse. Various mechanisms for monolayer collapse and the resulting reorganization of the film have been proposed, and only a few studies have demonstrated the formation of a bilayer after collapse and with the use of a Ca²⁺ solution. In this work, Langmuir isotherms coupled with imaging ellipsometry and polarization modulation infrared reflection absorption spectroscopy were recorded to investigate the air–water interface properties of Langmuir films of anionic nucleolipids. We report for these new molecules the formation of a quasi-hexagonal packing of bilayer domains at a low compression rate, a singular behavior for lipids at the air–water interface that has not yet been documented