Synthesis and evaluation of cell-permeable analogs of trehalose

In the medical and research communities, the two most common methods for storing mammalian cells are freezing or drying. Unfortunately these processes can result in cellular damage that profoundly reduces cell viability. We have developed a new method for preserving mammalian cells that exploits the naturally occurring disaccharide trehalose. Found in yeast, bacteria, fungi, and insects, trehalose acts as a cellular protectant for these organisms when they are subjected to harsh conditions such as freezing and drying. While trehalose must be found inside the cell in order to be effective, the hydrophilicity of this disaccharide inhibits its ability to cross the mammalian cell membrane. To overcome this obstacle, we have synthesized hydrophobic trehalose analogs which are cell-permeable. We have demonstrated that these analogs deliver trehalose into mammalian cells and have quantified the intracellular trehalose concentrations from cells that have been incubated with these analogs. Currently, we are evaluating the protective effects of these trehalose analogs. Results from these studies will eventually lead to a more effective method for preserving live mammalian cells.