Edbert Chung

Professor Mark Von Itzstein, Glycomics and Computational

Chemistry
Professor Mark von Itzstein is an Australian scientist working in the field of
organic chemistry, and more specifically the field of glycoscience/ Glycomics. He has
accomplished much in his field or study and continues to work towards new groundbreaking research in the development of treatments and vaccines for a number of
diseases. Professor Itzstein completed his PhD in organic chemistry at Griffith
University in 1984. Mark has international standing in glycoscience and drug
discovery and is most famous for his participation in the synthesis of Zanamivir (sold
under the name Relenza) a neuraminidase inhibitor used in the treatment and
prophylaxis of influenza.
The study of Glycomics focuses on the research and discovery of the role
carbohydrates play in disease and ageing. Using that knowledge carbohydrate-based
drugs (glycopharmaceuticals) can be synthesised to interfere with the carbohydraterelated biological process of disease, effectively slowing the spread of a disease
through the body and/or killing it off. The science has the potential to cure or help
treat a variety of diseases such as cancer, arthritis, multiple sclerosis, food poisoning
and infectious diseases such as cholera, tuberculosis, melioidosis, influenza and
malaria.
Professor Mark von Itzstein cemented himself as a major contributor to his field
with his study into influenza (commonly known as the flu), an illness categorised by
its ability to constantly mutate to become unrecognisable to the human immune
system and can repeatedly infect millions of people; the strain evading irradiation.
The structure of the influenza virus had long been known. It's essentially a
package of genes enveloped by two proteins: sialidase and haemagglutinin.
Haemagglutinin allows the virus to attach to and pierce a cell membrane. Once inside
the cell, the virus multiplies and produce millions of new particles called virions. The
sialidase proteins then help release the virions which infect the upper respiratory
tract leading to the appearance of the symptoms of influenza.
For a long time the general consensus was that any cure for influenza should
focus on disabling the ability of haemagglutinin to attack and enter the bodys cells.
When Professor Mark entered the investigation he and his group began to focus on
whether the protein sialidase had any characteristic that remained constant with all
influenza strains. Using the process of Computational chemistry they modelled and
determined that the key to a cure laid in the development of an inhibitor which would
disable the sialidase proteins.
Computational Chemistry is a branch of chemistry that uses principles of
computer science to assist in solving chemical problems. It uses the results gained
from theoretical chemistry, incorporated into efficient computer programs, to
calculate the structures and properties of molecules and solids. While its results

Edbert Chung
normally complement the information obtained by chemical experiments, it can in
some cases predict unobserved chemical phenomena. It is widely used in the design
of new drugs and materials and was utilized by Marks team to
simulate a number of compounds firstly to determine the
shape
and nature of the sialidase protein, then to observe certain static
characteristics of its composition and finally to build models which
would represent possible inhibitors before synthesis. The team
utilized available computer technology to support their search
without
the need to constantly synthesis substances to test their possible
use;
instead inputting potential drug/cures molecule structures into
advance
programs and simulating the resulting effect.
Eventually this lead to the synthesis of a simple inhibitor of the sialidase
protein. This inhibitor, which he named 2-deoxyNeu5Ac, proved to be effective in
tests on laboratory animals. This lead to further success and eventually his team had
developed a drug which he describes as not designed to kill the virus. It slows it
down so that the immune system can deal with it. The final product Relenza has
been approved for the treatment of influenza worldwide.
The discovery is considered to be a significant outcome and notable
contribution in glycotherapeutic drug development in the last century and has further
consolidated the potential of using carbohydrates as drugs and carbohydraterecognising proteins as drugs to target diseases. Dr von Itzstein moved on to the
working on anti-cancer agents based on the strategies devised during his influenza
work and continues to work in the field of glycoscience as well as heading the
Institute for Glycomics at Griffith University that Mark established in 2000.