Date of Award

12-2009

Degree Type

Thesis

Degree Name

Master of Science

Major

Chemistry

Major Professor

Michael Best

Committee Members

David Baker, Frank Vogt

Abstract

Carbohydrate–protein interactions play vital roles in various biochemical processes such as signal transduction and cell surface recognition events. The clustering of carbohydrates into dense domains such as lipid rafts regulates recognition by multivalent receptors (i.e. lectins). These regions are known to play important roles in biological processes such as cellular transduction and trafficking. In order to characterize the clustering of glycans on cell surfaces, detection of domains with high carbohydrate density is of great interest. In this thesis, we present the work based on a modular strategy to design and synthesize boronic acid-based carbohydrate receptors, which are termed as boronolectins because of their similarly in functions with lectins, in order to understand the molecular basis of carbohydrate–protein interactions. These receptors will then be employed for binding studies with carbohydrate based guests and catechol derivatized diol target molecules in order to study the binding interactions between the boronic acid receptors and diol moieties present in guest molecules.

A second project that is described in this thesis is based on developing diacylglycerol-based lipid probes, which could be employed for studying protein-lipid binding interactions. Due to involvement of protein-lipid binding interactions in the onset of various pathophysiological conditions, it is of paramount importance to investigate these interactions at the molecular level. DAG (diacylglycerol) represents an important class of signaling lipids and members of the Protein kinase C (PKC) family are described as the main responsive receptors of DAG. PKCs are known to be involved in tumorigenesis. In order to elucidate the exact correlation between PKC activity and carcinogenesis, it will be beneficial to design and synthesize DAG-based lipid analogs. In this thesis, hence, a modular strategy to design and synthesize a class of DAG-based lipid analogs by appending reporter groups such as polyaromatic fluorophores in the sn-1 acyl chains via the traceless Staudinger ligation is described.

In both the projects, the synthetic strategy adopted is based on a modular design in order to generate a common scaffold which undergoes modification at the last step to generate a class of fluorophore tagged analogs to be employed for studies.

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