Synthesis and characterization of a novel carbohydrate-based supramolecular structure

Conventional glycerol based phospholipids such as phosphocholines form spherical self-closed structures called liposomes. Previous research includes extensive modification of both the head and tail groups. Modification of the glycerol backbone (A) (Figure 1)* however, has been limited. We have synthesized and characterized a novel class of carbohydrate-based phospholipid where the glycerol backbone of the phospholipid is replaced by 1-methoxy ribose to form, for example, bis-(2,3-acyl)-1-methoxy-5-(phosphocholine) ribose (B) (Figure 1)*. We have performed this modification for two reasons. First, from a basic science standpoint, we were interested in observing the effect of backbone modification upon bilayer structures. Second, from a biotechnological standpoint, the 1-position on the ribose ring (*) provides an important synthetic handle for additional chemical modification. With this handle, phospholipid derivatization at a non-head group site is made possible.; We have named this new class of phospholipid self-assemblies ‘Carbohydrosomes’ since their constituent lipids are built upon carbohydrate backbones. With this modification in molecular structure, we observe a change in the physical properties of the bilayer structure with modulated differential scanning calorimetry and X-ray diffraction, such as an increase in phase-transition temperature and more ordered bilayer packing. Dimyristoyl ribo-phosphocholine is stable to phospholipase A₂ activity; however, it is not an inhibitor of this enzyme. We have demonstrated that carbohydrate-based phospholipids mix with glycerol-based phospholipids by observing a single intermediate phase-transition peak. This experiment indicates doping small amounts of modified phospholipid into bilayers is possible. Further studies utilizing 1-position modified lipids will provide further insight into bilayer packing as well as molecules useful for biotechnological applications. Both cationic and anionic carbohydrate-based phospholipids have also been synthesized and characterized drug and gene delivery.; *Please refer to dissertation for diagrams.