Download the full-sized PDF of Design and synthesis of inhibitors for the human neuraminidase 3 enzymeDownload the full-sized PDF



Permanent link (DOI):


Export to: EndNote  |  Zotero  |  Mendeley


This file is in the following communities:

Graduate Studies and Research, Faculty of


This file is in the following collections:

Theses and Dissertations

Design and synthesis of inhibitors for the human neuraminidase 3 enzyme Open Access


Other title
DANA derivatives
neuraminidase inhibitors
human neuraminidase
Type of item
Degree grantor
University of Alberta
Author or creator
Zou, Yao
Supervisor and department
Cairo, Christopher W. (Chemistry)
Examining committee member and department
Hall, Dennis G. (Chemistry)
Schieber, Andreas (Agricultural, Food & Nutritional Science)
Department of Chemistry

Date accepted
Graduation date
Master of Science
Degree level
Sialidase enzymes play an important role in regulation of cellular activities by hydrolyzing the terminal, non-reducing sialic acids attached to various glycolipids, glycoproteins, and gangliosides. The family of human sialidase enzymes, NEU1, NEU2, NEU3, and NEU4 contribute specifically to different cellular processes. In particular, the plasma membrane associated sialidase NEU3 was studied by our group due to its specificity for glycolipids and its proposed role in cell signaling. This thesis describes the design and synthesis of sialidase inhibitors based on the 2,3-didehydro-N-acetyl neuraminic acid scaffold. Specific inhibitors of these enzymes will allow us to explore their function in vivo. In Chapter 2 we describe a series of C9 and N5Ac modified analogs of DANA (2,3-Didehydro-2-deoxy-N-acetylneuraminic acid) which were designed, synthesized and biologically evaluated. Molecular docking experiments revealed NEU3 can tolerate large hydrophobic groups at the C9 position, however, N5Ac derivatives failed to inhibit NEU3. This result suggested that glycerol side-chain modified derivatives of DANA could prove to be potent inhibitors of the enzyme. In Chapter 3 we develop a synthetic route to generate a series of C7-modified DANA derivatives. We isolated several C7-hydrazone derivatives that will be tested against human neuraminidase enzymes as inhibitors. The results from these studies provided valuable insight regarding the interaction of small molecule inhibitors with the active site of the human NEU3 enzyme, and have improved synthetic strategies towards DANA derivatives that may take advantage of the unique active site topology of NEU3.
Permission is hereby granted to the University of Alberta Libraries to reproduce single copies of this thesis and to lend or sell such copies for private, scholarly or scientific research purposes only. Where the thesis is converted to, or otherwise made available in digital form, the University of Alberta will advise potential users of the thesis of these terms. The author reserves all other publication and other rights in association with the copyright in the thesis and, except as herein before provided, neither the thesis nor any substantial portion thereof may be printed or otherwise reproduced in any material form whatsoever without the author's prior written permission.
Citation for previous publication
Zou, Yao (2010). Bioorganic & Medicinal Chemistry Letters.

File Details

Date Uploaded
Date Modified
Audit Status
Audits have not yet been run on this file.
File format: pdf (Portable Document Format)
Mime type: application/pdf
File size: 8213638
Last modified: 2015:10:12 13:28:46-06:00
Filename: Zou_Yao_Fall 2011.pdf
Original checksum: 04ce68d9f458a4214ef8e3b00be5aeb4
Well formed: false
Valid: false
Status message: Invalid page tree node offset=271721
Status message: Invalid object number or object stream offset=8155777
Status message: Invalid Annotation list offset=8155777
Status message: Outlines contain recursive references.
File title: 1.pdf
Activity of users you follow
User Activity Date