Molecular recognition in supramolecular structures formed by phosphatidylnucleosides-based amphiphiles

Abstract

Supramolecular structures (micelles and vesicles) formed by a novel group of functionalized synthetic phospholipid amphiphiles, where the phospholipid group is connected to a nucleobase, have been studied with circular dichroism (CD), UV-Vis spectroscopy, and scattering techniques (quasi-elastic light scattering, QELS, and small angle neutron scattering, SANS). Base–base interactions in water at the vesicles or micellar surface exhibit recognition characteristics typical of linear polynucleotides (DNA, RNA, peptide nucleic acid (PNA)), suggesting that the supramolecular structure formed by the self-assembling of the phospholipids can replace the sterical support provided by the covalent skeleton in nucleic acids or PNA. In particular, vesicles and micellar solutions of di-alkyl -sn-glycero-phospho-adenosine, -uridine, and -cytidine were investigated. The 1/1 mixture of the complementary adenosine/uridine bases show molecular recognition in aqueous medium and at physiological pH, while the non-complementary adenosine/cytidine bases fail to give recognition. Small angle neutron scattering of micellar solutions of di-octanoyl-derivatives show that the recognition process is associated with a decrease of the mean area per polar head group while the aggregation number and the micellar shape remain unchanged. These results demonstrate that it is possible to reproduce in aqueous environment and with ‘primitive supramolecular systems’ the recognition processes that usually occur in complex molecules as DNA, RNA or the synthetic PNA.