Publication Date

Summer 2017

Degree Type

Thesis

Degree Name

Master of Science (MS)

Department

Chemistry

Advisor

Marc d'Alarcao

Keywords

Hybrid Inositol Glycan, Inositol Glycan, Insulin signaling, Synthesis, Type 2 diabetes

Subject Areas

Organic chemistry

Abstract

Inositol phosphate glycans (IPGs) are natural pseudo-oligosaccharides that are produced in some mammalian cells upon stimulation by insulin. IPGs are capable of inducing insulin-like effects in insulin sensitive cells, making them viable drug targets for treating type II diabetes. However, the synthesis of highly insulin-mimetic synthetic IPGs is inefficient, requiring more than fifty steps. The development of hybrid inositol glycans (HIGAs) has mitigated this problem. HIGAs consists of a commercially available non-carbohydrate moiety that is coupled with a saccharide group that requires only fifteen steps to synthesize. HIGAs are thus much more efficient to synthesize on large scales. This thesis describes the attempted synthesis of a library of HIGAs. The goal was to link five non-carbohydrate moieties to an IPG-like disaccharide via thiol-linkage. Three of the five non-carbohydrate moieties were negatively charged while the other two were neutral to study the effect that the negative charge has on the insulin-like activity of the HIGAs. The insulin-like activity can be quantified using a glucose uptake assay in cultured murine adipocytes. Unfortunately, the syntheses of the HIGAs were not completed but a novel precursor compound has been synthesized.

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