Electronic Theses and Dissertations

Date of Award

2013

Document Type

Thesis

Degree Name

M.S. in Pharmaceutical Science

Department

Biomolecular Sciences

First Advisor

Daneel Ferreira

Second Advisor

Marc Slattery

Third Advisor

Jordan K. Zjawiony

Relational Format

dissertation/thesis

Abstract

Complex carbohydrates from plant sources, such as the fruits of cranberry (Vaccinium macrocarpon Aiton), promote human health in a variety of ways. However, complete studies of carbohydrate function often hinge on a detailed understanding and thorough elucidation of the chemical structure. Several methods have been used in the structure elucidation of cranberry oligosaccharides, such as derivatization folloby analysis using gas chromatography-mass spectrometry (GC-MS). In this manner, the identity and quantity of glycosyl units within two cranberry oligosaccharides were investigated through hydrolysis of the oligomers and subsequent synthesis of trimethylsilyl and alditol acetate derivatives. Further analysis using partially methylated alditol acetate derivatives revealed the linkage position on each glycosyl unit. A complete structure was assembled through the compilation of data from the analysis of 1D and 2D NMR experiments yielding two novel oligosaccharides, the heptasaccharide β-D-glucopyranosyl-(1→4)-[α- D-xylopyranosyl-(1→6)]-β-D-glucopyranosyl-(1→4)-β- D-glucopyranosyl-(1→4)-[α-L-arabinofuranosyl-(1→2)-α- D-xylopyranosyl-(1→6)]-β-D-glucopyranose (1) and the octasaccharide β-D-glucopyranosyl-(1→4)-[α- L-arabinofuranosyl-(1→2)-α-D-xylopyranosyl-(1→6)]-β- D-glucopyranosyl-(1→4)-β-D-glucopyranosyl-(1→4)-[α- L-arabinofuranosyl-(1→2)-α-D-xylopyranosyl-(1→6)]-β- D-glucopyranose (2). Cranberry products are known to contain several biological activities, such as antioxidant properties, antiproliferative properties against several cancer cell lines, and antimicrobial and antiviral properties. In addition, several clinical trials and in vitro analyses have assessed the ability of cranberry products and extracts to aid in the treatment of urinary tract infections via prevention of adhesion of bacteria to uroepithelial cells. Cranberry extracts enriched with oligosaccharides, including compounds 1 and 2, were assessed for biological activity. Bioassays included an antimicrobial screen against 10 different pathogenic organisms, a breast cancer cell viability assay, and an anti-adhesion assay involving Escherichia coli and human uroepithelial cells. While antimicrobial, anticancer, and anti-adhesion activity was not confirmed for purified compounds 1 and 2, the parent fraction exhibits activity which prevents the adhesion of P-fimbriated E. coli to uroepithelial cells. This activity suggests the importance of oligosaccharide-enriched fractions in the anti-adhesion activity of cranberry products.

Concentration/Emphasis

Emphasis: Pharmacognosy

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