Publication Date

Summer 2014

Degree Type

Thesis

Degree Name

Master of Science (MS)

Department

Chemistry

Advisor

Marc d'Alarcao

Keywords

Inositol Glycan

Subject Areas

Chemistry

Abstract

A 2010 study by Centers for Disease Control and Prevention has projected that one of three US adults could have diabetes by the year 2050. More than 90% of the diagnosed cases are Type II diabetes, a condition characterized by insulin resistance. In search of new antidiabetic drugs, a class of natural, phosphorylated, inositol-containing pseudosaccharides called inositol glycans (IGs) has been studied for years. These compounds have insulin-mimetic activity in insulin-sensitive cells and can stimulate processes such as lipogenesis and glucose transport. Due to the heterogeneity of IGs, it is very difficult to isolate them from their natural sources, and the potent synthetic ones are complex structures demanding lengthy and laborious chemistry.

It has been observed that a hybrid IG, an inositol-containing disaccharide conjugated with a non-carbohydrate fluorophore, exhibits relatively high insulin-mimetic activity. We propose the generation of a library of similar hybrid IGs (HIGAs), via a relatively short synthetic pathway, in which each HIGA is prepared from the attachment of the phosphorylated inositol core to a readily available non-carbohydrate piece. The ability of each HIGA to activate insulin-sensitive cells will be assayed to identify the ones with maximum insulin-like response. The active HIGAs would be further studied in future research as potential pharmaceutical agents for treatment of diabetes.

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