Grinstaff Group - BME/Chemistry - Boston University

Supramolecular Assemblies of Nucleoside-based Amphiphiles

The synthesis of supramolecular systems using weak noncovalent chemical bonds to assemble molecules is an important and increasingly successful strategy. These supramolecular assemblies represent diverse structures and span length scales from a few nm to mm. Elucidation and control of the factors that govern the recognition events at the molecular level represent a significant advantage to construct functional or intricate systems. To this end, our interest is in using increasingly complex molecules capable of forming programmable supramolecular systems. Nucleolipids possessing both nucleic acid recognition and lipophilic chains components are emerging as building blocks for constructing such assemblies because these amphiphiles possess a diversity of functional groups capable of cooperative non-covalent interactions combined with specific base-base recognition.

We have synthesized a wide range of chemical diverse cationic, neutral, and ionic nucleolipids as shown in the Figure. We have used these nucleolipids to form nanofibers and gels, as well as supramolecular complexes with nucleic acids for gene transfection.

Recently, we reported the formation of self-assemblies resulting from the interactions of complementary ketal based adenosine (6 (2’,3’-O-16-hentriacontanyliden-adenosine-5’-phosphocholine, PAPC) and uridine (uridine 3 (2’,3’-O-16-hentriacontanyliden-uridine-5’-phosphocholine, PUPC) nucleolipids. Separately, lipids PUPC and PAPC exist in a fluid state at room temperature, and as noted above, organize into lamellar systems upon hydration. However, when the two complementary lipids are hydrated in close proximity to each other, a new supramolecular structure spontaneously forms at the interface in a few seconds. For this experiment, solid PUPC and PAPC are loaded on a glass slide opposite each other and separated by a distance of 0.5 mm. Real time photographs show that upon hydration, the two lamellar systems approach each other and upon contact form a wall of vesicles at the interface. Numerous small vesicles 50 µm are present in this wall of vesicles as well as fusions with larger ones. The molecular recognition and vesicular formation event occur relatively rapidly (see Figure).

Selected Publications

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